Cancer Cell International最新文献

{"title":"Comparison of local effects and systemic T-cell responses in patients with breast cancer treated by radiofrequency ablation versus microwave ablation.","authors":"Muxin Yu, Bangjie Wang, Ying Qu, Wen Sun, Mengdi Liang, Xinrui Mao, Yunshan Jiang, Jiaming Wang, Xinyu Tang, Hong Pan, Yi Zhao, Hui Xie, Qiang Ding, Shui Wang, Wenbin Zhou","doi":"10.1186/s12935-025-03896-7","DOIUrl":"10.1186/s12935-025-03896-7","url":null,"abstract":"<p><strong>Background: </strong>Radiofrequency ablation (RFA) and microwave ablation (MWA) have been investigated as treatments for early-stage breast cancer. However, it is unclear which minimally invasive thermal therapy demonstrates superior local efficacy. Also, the cytolytic functions of peripheral T cells after thermal ablation in solid tumors have not been reported.</p><p><strong>Materials and methods: </strong>In this study, 60 patients with breast cancer were enrolled from two clinical trials conducted between March 2020 and December 2021. The local effect of thermal ablation evaluated through pathological examinations or radiological imaging was the primary outcome. The secondary outcome involved systemic T-cell responses. Peripheral blood samples were collected before and after treatments. The ablation-induced immune responses were analyzed using flow cytometry, enzyme-linked-immunosorbent assay (ELISA), quantitative real-time PCR (qRT-PCR) and single-cell RNA sequencing.</p><p><strong>Results: </strong>Both RFA and MWA showed favorable local effects in the treatment of breast cancer. Compared to surgery, RFA increased peripheral CD8 + T-cell proportions but did not enhance their cytolytic functions. Conversely, MWA induced stronger cytolytic functions of peripheral T cells and upregulated memory CD4 + T cells. The distinct immune responses induced by MWA and RFA were associated with variations in antigen presentation pathways, types of antigen-presenting cells (APCs), and cytokine secretion profiles. Single-cell RNA sequencing further revealed that dendritic cells were the APCs activated by MWA, exhibiting upregulated fatty acid metabolism.</p><p><strong>Conclusion: </strong>Both thermal ablation therapies are technically feasible for early-stage breast cancer. However, MWA appears superior in enhancing the cytolytic functions of peripheral T cells compared to RFA. This study provides the first mechanistic insight into the different immune responses induced by MWA and RFA, although future clinical trials are necessary to validate these findings.</p><p><strong>Trial registration: </strong>ChiCTR2000029665. Registered February 09, 2020 ( https://www.chictr.org.cn/showproj.html?proj=48315 ) and ChiCTR2000029155. Registered January 16, 2020 ( https://www.chictr.org.cn/showproj.html?proj=48314 ).</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"261"},"PeriodicalIF":5.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chimeric Antigen Receptor (CAR)-NK92 cells effective against glioblastoma, breast- and pancreatic cancer in vitro and in a murine xenograft model of ovarian cancer.","authors":"Abdelhadi Boulifa, Alexander Sebastian Franzén, Martin J Raftery, Clarissa Radecke, Gabriele Pecher","doi":"10.1186/s12935-025-03865-0","DOIUrl":"10.1186/s12935-025-03865-0","url":null,"abstract":"<p><strong>Background: </strong>Aggressive tumors such as glioblastoma, breast, ovarian and pancreatic cancer have low survival rates and new therapies are urgently needed. One potential target is CD44v6, a splice variant of CD44 that is associated with poor prognosis. Recently, NK cells expressing CAR molecules have shown promise in combining specific targeting of solid tumors with a low risk of side effects. The aim of the current study is to explore the efficacy of the CD44v6-CAR construct expressed in the NK cell line NK92 against solid tumors both in vitro and in vivo.</p><p><strong>Methods: </strong>Flow cytometry was used to evaluate the expression of CD44v6 on glioblastoma, breast, ovarian and pancreatic cancer cell lines. In order to investigate the efficacy of CD44v6-CAR-NK92 against these solid tumors in 2D and 3D models, cytotoxicity was measured using a luminescent cell viability assay. Additionally, we assessed the levels of IFN-γ in cell culture supernatants using an ELISA method. Finally, we evaluated our therapeutic in vivo using a xenografted murine model of ovarian cancer through bioluminescent imaging.</p><p><strong>Results: </strong>CD44v6-CAR-NK92 cells exhibit specific cytotoxicity against glioblastoma, breast, ovarian and pancreatic cancer after 24 h compared to the control, both in 2D and 3D models. Furthermore, the activity of CD44v6-CAR-NK92 was validated by quantifying specific cytokine release in response to target cells. Finally, we could show that CD44v6-CAR-NK92 was effective in reducing tumor burden in a xenografted murine model of ovarian cancer.</p><p><strong>Conclusion: </strong>Our results demonstrate that CD44v6-CAR-NK92 cells could be an attractive therapeutic agent for the treatment of solid tumors.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"260"},"PeriodicalIF":5.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One step further in targeting acute leukemia by combining antibody-based immunotherapies and small molecule inhibitors.","authors":"Armin Dozandeh-Jouybari, Erfan Rohaninia, Sara Faaliat, Nazanin Joudaki, Sara Ghandi, Maryam Talebi Moghaddam, Saeid Taghiloo, Tohid Kazemi","doi":"10.1186/s12935-025-03869-w","DOIUrl":"10.1186/s12935-025-03869-w","url":null,"abstract":"<p><strong>Background: </strong>Acute leukemia is a bone marrow-related disease characterized by fast progression and the production of immature blood cells rather than normal ones that are classified as either acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Chemotherapy as a conventional treatment has many side effects, thus new medications that target intracellular molecules and cell surface markers on leukemic cells have been developed in the last decades.</p><p><strong>Main body: </strong>This review focuses on antibody-based targeted treatments, which so far, have been shown to improve the treatment outcomes, including the immune checkpoint inhibitors (ICIs), monoclonal antibodies, and bispecific T-cell engagers (BiTE). Other classes are small molecule inhibitors (as a new generation of chemotherapeutic drugs in targeted therapies) that are discussed herein include SMIs of intracellular target molecules, including tyrosine kinases, serine/threonine kinases, BCL-2, and smoothened (SMO). These inhibitors have been very effective in dealing with certain genetic changes besides blocking the important cell molecules in acute leukemia responsible for the failure of the immune system. A focus is made on assessing the use of antibody-mediated therapies in combination with SMIs for treating acute leukemia.</p><p><strong>Short conclusion: </strong>Given the distinct mechanisms and objectives of these two therapeutic modalities that have the potential to synergistically enhance one another, along with the findings from clinical trial investigations, it appears that combination therapy may yield superior efficacy compared to monotherapy, representing a progressive advancement in the treatment of acute leukemia.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"254"},"PeriodicalIF":5.3,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STIM1 signaling modulates invasive phenotypic plasticity by regulating calpain-dependent cleavage of integrin-β4 in nasopharyngeal carcinoma cells.","authors":"Weiming Deng, Wenlin Huang, Yujuan Huang, Lihong Huang, Linsong Ye, Fei Liu, Min Li, Jingjin Weng, Qian He, Jinyan Zhang, Shenhong Qu, Jiazhang Wei","doi":"10.1186/s12935-025-03890-z","DOIUrl":"10.1186/s12935-025-03890-z","url":null,"abstract":"<p><strong>Background: </strong>Stromal interaction molecule 1 (STIM1)-mediated Ca²⁺ signaling modulates the malignant features of nasopharyngeal carcinoma (NPC), a unique Epstein-Barr virus (EBV)-associated human malignancy. Integrin-β4 is involved in EBV-promoted motility in NPC cells. However, the underlying mechanism through which STIM1 signaling manipulates the invasive characteristics of NPC cells and the implication of integrin-β4 remains elusive. The present study aimed to characterize the role of integrin-β4 in the phenotypic plasticity for the epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT and MET), and determine whether STIM1 signaling enhances invasive potential by modulating integrin-β4 cleavage in NPC cells.</p><p><strong>Methods: </strong>Western blotting of epithelial and mesenchymal markers, cell migration and colony formation assays were performed to evaluate the EGF-stimulated EMT and laminin-induced MET in vitro. A zebrafish xenograft model was employed to elucidate the proliferation of transplanted NPC cell spheroids in vivo. A tail vein injection-lung metastasis mouse model was utilized to determine the capacity for distant metastatic colonization of NPC cells. Immunohistochemical analysis was conducted to detect the expression level of integrin-β4 in NPC tissues.</p><p><strong>Results: </strong>Integrin-β4 was required for the bi-directional epithelial-mesenchymal transition in NPC cells. Silencing of integrin-β4 inhibited cell migration and clonogenicity in vitro, reduced clonal expansion of tumor cell clusters in zebrafishes, and eliminated distant metastatic colonization in mice. STIM1 Ca²⁺ signaling modulated the redistribution of integrin-β4 in migrating NPC cells. Mechanistically, STIM1-mediated Ca²⁺ influx enhanced aggregation of integrin-β4 at the cell membranes by promoting the calpain-dependent cleavage of integrin-β4. Clinically, we confirmed that integrin-β4 was highly expressed in primary tumors and cervical lymph node metastases.</p><p><strong>Conclusion: </strong>STIM1 signaling promotes invasiveness by enabling accelerated subcellular integrin-β4 redistribution, which is essential for maintaining the invasive plasticity of NPC cells.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"253"},"PeriodicalIF":5.3,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Molecular and phenotypic characterization of 5-FU resistant colorectal cancer cells: toward enrichment of cancer stem cells.","authors":"Amirhesam Babajani, Saeed Rahmani, Mohammad Jamal Asadi, Elmira Gheytanchi, Glavizh Adibhesami, Faezeh Vakhshiteh, Zahra Madjd","doi":"10.1186/s12935-025-03891-y","DOIUrl":"10.1186/s12935-025-03891-y","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"252"},"PeriodicalIF":5.3,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIF-1α and HIF-2α: synergistic regulation of glioblastoma malignant progression during hypoxia and apparent chemosensitization in response to hyperbaric oxygen.","authors":"Pan Wang, Sheng Gong, Bin Liao, Jie Liu, Lu Zhao, Nan Wu","doi":"10.1186/s12935-025-03823-w","DOIUrl":"10.1186/s12935-025-03823-w","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM), the most malignant type of brain tumour, is regulated mainly by a hypoxic microenvironment. Previous studies have focused mainly on the effects of hypoxia inducible factor-1α (HIF-1α) or hypoxia inducible factor-2α (HIF-2α) alone on GBM, and the results have shown that each factor regulates the malignant progression of GBM, but the single knockout of either gene does not markedly influence this regulation. This study was performed to determine whether HIF-1α and HIF-2α synergistically regulate the malignant progression of GBM. Therefore, HIF-1α and HIF-2α were knocked out in GBM cells. Compared with single HIF-1α- or HIF-2α-knockout and control cells, cells with simultaneous knockout of HIF-1α- and HIF-2α presented significantly greater changes, including differential gene expression and changes in biological process, cellular component, and molecular function GO terms, and enriched KEGG pathways. In addition, dual-knockout cells were induced to transition to G₂/M + S phase, exhibiting the greatest growth rate but the lowest degree of stemness and invasion; after temozolomide (TMZ) treatment, the dual-knockout cells exhibited the greatest rate of apoptosis and lactate dehydrogenase (LDH) release and the lowest growth rate and tumour size and weight, resulting in the longest survival time. Hyperbaric oxygen (HBO) is an effective method for alleviating GBM-related hypoxia; we investigated phenotypic changes in HBO-treated cells and observed increased growth rates but decreased HIF-1α and HIF-2α expression and a decreased degree of stemness. After TMZ exposure, HBO-treated cells presented increased apoptosis rates and LDH release and decreased tumour size and weight, resulting in increased survival. These results suggest that HIF-1α and HIF-2α together exhibit synergistic regulation and play major regulatory roles in GBM. Simultaneous targeting of both HIF-1α and HIF-2α with TMZ is an important method for treating GBM patients and improving patients' prognosis. Therefore, HBO can be used in GBM treatment because of its ability to sensitize cells to chemotherapy via the significant inhibition of both HIF-1α and HIF-2α expression.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"251"},"PeriodicalIF":5.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MYO1B promotes radioresistance in head and neck squamous cell carcinoma by regulating tumor stemness and DNA damage repair via the PI3K/AKT pathway.","authors":"Yanan Li, Jiahao Liu, Zhen Wang, Yilei Zhang, Baiying Liu, Ling Chu","doi":"10.1186/s12935-025-03863-2","DOIUrl":"10.1186/s12935-025-03863-2","url":null,"abstract":"<p><p>Head and Neck Squamous Cell Carcinoma is a prevalent malignancy characterized by high recurrence rates. While surgery remains the primary treatment, postoperative radiotherapy is essential for preventing tumor recurrence. However, the mechanisms driving radiotherapy resistance in HNSC remain largely unknown. With a multi-layered approach encompassing bioinformatics analysis, clinical tissue sample validation, in vitro and in vivo experiments, we discovered that MYO1B played a critical role in radiotherapy resistance of HNSC. Our findings underscored that MYO1B was significantly overexpressed in HNSC tissues and was associated with poor prognosis, particularly in patients undergoing radiotherapy. Functional investigations revealed that knockdown of MYO1B reduced the expression of stemness markers (SOX2, OCT4), decreased EMT-related protein levels, inhibited the phosphorylation of the key DNA damage repair protein ATM and increased sensitivity to radiotherapy. Mechanistically, knockdown of MYO1B inhibited the PI3K/AKT signaling pathway to reduce the expression of stemness-and DNA damage repair-related genes, and the use of an AKT activator reversed the observed reductions in tumor stemness and radiotherapy resistance. In vivo, MYO1B knockdown led to reduced tumor growth and enhanced radiotherapy sensitivity in a xenograft model. Clinical sample validation discovered that MYO1B was associated with disease-free survival, potentially due to higher tumor stemness and lower CD8 + cell infiltration. In summary, our study provides novel insights into the role of MYO1B in HNSC and highlights its potential as a therapeutic target for overcoming radiotherapy resistance.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"248"},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Petiveria alliacea and Caesalpinia spinosa extracts reduce the generation of cancer-associated fibroblasts in a 3D platform representative of the tumor microenvironment.","authors":"María Camila Jimenez, Paola Lasso, Susana Fiorentino, Alfonso Barreto","doi":"10.1186/s12935-025-03860-5","DOIUrl":"10.1186/s12935-025-03860-5","url":null,"abstract":"<p><strong>Background: </strong>The tumor microenvironment (TME) is a complex network of cellular and acellular participants, each of which contributes to ensuring tumor growth. Cancer-associated fibroblasts (CAFs) represent a key TME population that actively participates in stromal remodeling and metabolic coupling with tumors, significantly favoring both the process of carcinogenesis and the establishment of metastasis. Therefore, developing therapies that target CAFs constitute valuable therapeutic alternatives. However, efficiently modeling the generation of CAFs in the tumor microenvironment is challenging.</p><p><strong>Methods: </strong>We constructed a 3D structure of the tumor microenvironment (TME), which we refer to as \"TME spheroids\". These spheroids are composed of 4T1 murine breast cancer cells and 3T3 murine fibroblasts, allowing us to mimic the development of a cancer-associated fibroblast (CAF) phenotype. This novel 3D model serves as a platform for evaluating the impact of two natural extracts on TME interactions and their ability to impede tumor progression.</p><p><strong>Results: </strong>Using the TME-spheroid model, we tested the effects of two extracts on CAF generation: Anamu-SC obtained from Petiveria alliacea and P2Et from Caesalpinia spinosa. Both extracts disrupted the interaction between tumor cells and fibroblasts, reducing the ability of CAFs to support tumor growth and spread.</p><p><strong>Conclusions: </strong>We found that the two extracts interfere with circuits that drive tumor-fibroblast crosstalk, attenuating the phenotype and functional activities associated with CAFs in this TME model.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"243"},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory mechanisms and clinical implications of PIWI-interacting RNAs (piRNAs) in major digestive tract cancers.","authors":"Penghui Li, Yuan Xue, Xinyu Gu","doi":"10.1186/s12935-025-03889-6","DOIUrl":"10.1186/s12935-025-03889-6","url":null,"abstract":"<p><p>Cancers of the digestive tract, including those affecting the esophagus, stomach, liver, pancreas, and colorectum, impose a substantial global health burden due to their high morbidity and mortality rates. Despite advancements in diagnostic and treatment modalities, the molecular mechanisms underpinning the initiation and progression of digestive tract cancers remain incompletely understood. Recent progress in high-throughput sequencing technology has uncovered the crucial role of small non-coding RNAs (ncRNAs) in regulating gene expression and maintaining genomic stability across various cancers, including those affecting the digestive tract. P-element-induced wimpy testis (PIWI)-integrating RNAs (piRNAs), a subset of small ncRNAs, emerge as pivotal regulators in preserving genome integrity by suppressing transposable elements in germline cells. Growing evidence implicates piRNAs in the development and advancement of digestive tract cancers. Notably, piRNAs exhibit complex and multifaceted roles in these tumors, functioning as both tumor suppressors and oncogenes. They exert their effects through diverse mechanisms, including post-transcriptional gene silencing, epigenetic modifications, and modulation of signaling pathways involved in tumorigenesis, such as the Wnt/β-catenin, PI3K/Akt, and MAPK pathways. Dysregulation of piRNAs disrupts key cellular processes, including cell cycle regulation, apoptosis, epithelial-mesenchymal transition, and metastasis, across various digestive tract cancers. Moreover, distinct expression profiles of specific piRNAs correlate with diverse clinical features and outcomes in individuals afflicted with digestive tract cancers, highlighting their potential as diagnostic and prognostic biomarkers in this context. Furthermore, therapeutic interventions targeting dysregulated piRNAs or their downstream effectors hold promise as novel avenues for precision medicine approaches in managing digestive tract cancers. In this review, we summarize the current understanding of piRNAs in digestive tract cancers, focusing on their dual roles as both tumor suppressors and oncogenes. We further delve into the intricate molecular mechanisms by which piRNAs modulate crucial cellular processes implicated in tumorigenesis. Additionally, we explore the potential of piRNAs as valuable diagnostic, prognostic, and therapeutic biomarkers in the landscape of digestive tract cancers. By elucidating the complex interplay between piRNAs and digestive tract cancers, this review aims to offer insights into novel therapeutic strategies centered around targeting piRNAs for precision medicine approaches in the management of these malignancies.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"244"},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination of astragalus polysaccharide with Diosbulbin B exerts an enhanced antitumor effect in BRAF^mut papillary thyroid cancer with decreased liver toxicity.","authors":"Shuai Xu, Qi Liang, Hang Li, Hai Zhou, Zhenyuan Xu, Yanjun Yan, Yue Zhang, Renqun Ye, Xujun You","doi":"10.1186/s12935-025-03853-4","DOIUrl":"10.1186/s12935-025-03853-4","url":null,"abstract":"<p><strong>Background: </strong>Diosbulbin B (DB) is a traditional Chinese medicine used for thyroid cancer treatment, but always brings severe liver injury. In the current study, we investigated the role of astragalus polysaccharide (APS) in DB-induced hepatotoxicity and their anti-tumor effect on BRAF^mut papillary thyroid cancer (PTC), and disclosed the underlying mechanisms.</p><p><strong>Methods: </strong>Two BRAF^mut PTC IHH-4 and GLAG-66 cell lines were applied for the in vitro assays. CCK-8, flow cytometry, transwell chambers, enzyme-linked immunosorbent assay (ELISA) and transmission electron microscopy (TEM) were performed for cell growth, apoptosis, migration/invasion, malondialdehyde (MDA)/glutathione (GSH) content and mitochondria damage detection. Human normal liver epithelial cell line THLE-2 was used to assess the liver toxicity, together with the animal experiment.</p><p><strong>Results: </strong>The IC50 of APS and DB in IHH-4 cells were 153.9 µg/mL and 41.2 µM, respectively, while they were 728.0 µg/mL and 22.74 µM in GLAG-66 cells. Combination of APS and DB enhanced the anti-cancer role of DB with increased cell apoptosis and LDH release, and weakened cell growth, migration and invasion capacities. Interestingly, the combination of these two drugs significantly alleviated the liver injury induced by DB. In mechanism, we found that APS combined with DB treatment triggered the increase of MDA level while decreased GSH level, and deteriorated mitochondria damage. Inhibition of ferroptosis impaired the anti-PTC role of APS combined with DB with no influencing on liver injury both in vivo and in vitro.</p><p><strong>Conclusions: </strong>In conclusion, our study shows the combined therapy strategy of APS and DB regimen achieves better anti-cancer response through increasing MDA level while decreasing GSH level. Importantly, the combined therapy of APS and DB significantly decreased the liver toxicity induced by DB. These findings suggest that APS combined DB is a potential therapeutic strategy for BRAF^mut PTC with high efficacy and low liver toxicity.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"245"},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}