Medical Oncology最新文献

{"title":"Nano-phytochemical-based formulations as promising opportunities for prostate cancer therapy and management: a comprehensive narrative review.","authors":"Mohammad Amin Bakhshan, Shaghayegh Sheikhzadeh, Mohammadreza Ramezanimoladehi, Mahtab Pourkamalzadeh, Sanaz Sheikhzadeh","doi":"10.1007/s12032-025-03059-8","DOIUrl":"https://doi.org/10.1007/s12032-025-03059-8","url":null,"abstract":"<p><p>Although traditional treatments such as chemotherapy and radiation are effective in the treatment of prostate cancer, they often cause significant side effects, leading to a search for alternative therapies. Phytochemicals show promise due to their strong anticancer properties and lower toxicity compared to conventional treatments. Nonetheless, their therapeutic potential is constrained by issues such as limited aqueous solubility and insufficient bioavailability, both of which reduce their absorption and diminish efficacy within the body. Recent progress in nanotechnology has overcome these challenges by creating nano-phytochemicals. Nanoscale drug delivery platforms enhance the aqueous solubility, chemical stability, and systemic bioavailability of plant-derived compounds. By enhancing their pharmacokinetics, nanotechnology allows for targeted delivery to prostate cancer cells, increasing therapeutic effectiveness. This innovation has redefined phytochemical-based cancer treatment, providing a solution to their previous limitations. Emerging studies reveal that nano-phytochemicals have diverse effects on prostate cancer cells. Research shows that these advanced formulations promote apoptosis (cell death), inhibit cell growth, and prevent metastasis in cancer progression. Additionally, combining phytochemicals with nanotechnology has demonstrated a synergistic effect, increasing prostate cancer cells' sensitivity to conventional treatments like chemotherapy and radiation. This strategy may offer safer and more efficacious therapeutic alternatives, thereby contributing to enhanced clinical outcomes for patients. In conclusion, the combination of phytochemicals and nanotechnology marks a significant breakthrough in prostate cancer therapy. This review discusses recent evidence on anti-prostate cancer effects of 12 phytochemicals (Hesperidin, Berberine, Curcumin, Quercetin, Caffeic acid, Apigenin, Epigallocatehin Gallate, Thymoquinone, Genistein, Resveratrol, Eupatorin, Fisetin, Epicatechin, Lupeol), in both free or nano-encapsulated forms, by focusing on their anticancer molecular pathways, in in vitro (types of prostate cancer cell lines) and in vivo (xenograft or other animal models), and clinical trials (completed or ongoing), as well as the synergistic interactions of these compounds with conventional chemotherapy and radiotherapy treatments.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"510"},"PeriodicalIF":3.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combinational therapy of cervical cancer consisting of probiotic particles and vincristine: a molecular in vitro study.","authors":"Abbas Asoudeh-Fard, Asghar Parsaei, Seyyedeh Mina Hejazian, Mohadeseh Asoudeh-Fard, Ahmad Gholami","doi":"10.1007/s12032-025-03071-y","DOIUrl":"https://doi.org/10.1007/s12032-025-03071-y","url":null,"abstract":"<p><p>Cervical cancer remains a major global health concern and ranks among the leading causes of cancer-related mortality in women. Although Vincristine Sulfate is a clinically established chemotherapeutic agent with potent anti-mitotic activity, its therapeutic utility is often restricted by dose-dependent toxicities and off-target effects. Recent evidence suggests that probiotics such as Lactobacillus fermentum may possess anti-tumor properties and could enhance the efficacy of conventional therapies. This study was designed to investigate whether co-administration of Lactobacillus fermentum could potentiate the anti-cancer effects of Vincristine Sulfate in HeLa cervical cancer cells, potentially allowing for a reduction in the effective chemotherapeutic dose. Lactobacillus fermentum was isolated from traditional dairy products and identified via molecular techniques. HeLa cells were treated with L. fermentum, Vincristine Sulfate, or a combination of both. Cell viability was assessed using the MTT assay, while apoptosis was quantified through Annexin V-FITC/PI staining and flow cytometry. Quantitative real-time PCR was employed to evaluate the expression of genes involved in apoptosis and the PI3K/AKT/mTOR signaling pathway. To evaluate the safety of bacterial treatment, L. fermentum was also tested on normal human umbilical vein endothelial cells (HUVECs) using the MTT assay. The half-maximal inhibitory concentrations (IC₅₀) were established at OD₆₀₀ = 0.5 (10 µL/mL) for L. fermentum and 10 µg/mL for Vincristine Sulfate in HeLa cells. Monotherapy with either agent led to a moderate reduction in cancer cell viability. However, the combination treatment (1 µg/mL Vincristine Sulfate + 10 µL/mL L. fermentum) significantly enhanced cytotoxicity, inducing a more profound decrease in cell viability and a marked increase in apoptotic cell populations. Gene expression analysis revealed upregulation of pro-apoptotic genes (PTEN, BAX, Caspase-3, -8, -9, Fas, IκB) and downregulation of survival-related genes (AKT, Bcl-2, mTOR) in the combination group compared to monotherapies. Importantly, L. fermentum had no significant cytotoxic effects on HUVECs, indicating selective targeting of cancer cells. Co-treatment with Lactobacillus fermentum and Vincristine Sulfate demonstrated a synergistic effect in HeLa cells, enhancing apoptosis and suppressing oncogenic signaling pathways, while enabling a tenfold reduction in Vincristine dosage. The lack of cytotoxicity in normal endothelial cells further underscores the therapeutic potential of this approach. These findings support the incorporation of probiotic-based adjuvants in cancer therapy to improve efficacy and reduce adverse effects. Future in vivo studies and clinical trials are warranted to validate the translational potential of this combinatorial strategy in cervical cancer management.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"509"},"PeriodicalIF":3.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PLK1 inhibition enhances gemcitabine-induced apoptosis through PLK1-dependent ERK1/2-Bim and AKT1/Noxa signals in pancreatic cancer cells.","authors":"Bing Lu, Hai Li, Dongfeng Deng, Yadong Wang","doi":"10.1007/s12032-025-03062-z","DOIUrl":"10.1007/s12032-025-03062-z","url":null,"abstract":"<p><p>Polo-like kinase 1 (PLK1) is a critical regulator of many cell cycle events, which has been found to be associated with resistance to cytotoxic drugs. In the present study, we investigates how PLK1 regulates the sensitivity of pancreatic cancer cells to Gemcitabine (GEM) and its mechanism. We detected the expression of PLK1 in pancreatic cancer tissues and cell lines and study the effects of PLK1 and Gemcitabine on cell viability and apoptosis of GEM-resistant pancreatic cancer PANC-1 cells and Gemcitabine sensitive BxPC-3 cells; Using inhibitors or siRNA, we further investigate the effects of PLK1 on ERK1/2, AKT1, and pro-apoptotic genes PUMA, Bim, and Noxa; We finally investigated the effect of the combined onvansertib and Gemcitabine on the growth of PANC-1 subcutaneous transplant tumors in nude mice and explored its possible mechanism of action. PLK1 is overexpressed in PDAC tissues and cell lines. Targeting PLK1 inhibits cell viability and induces cell apoptosis in PANC-1 cells in vitro by ERK1/2-dependent Bim and AKT1-dependent Noxa pathway. Gemcitabine activates ERK1/2 and AKT1, leading to acquired Gemcitabine resistance. Targeting PLK1 enhances Gemcitabine sensitivity in PANC-1 cells by upregulating ERK1/2-dependent Bim and AKT1-dependent Noxa expression in vitro. PLK1 re-expression by PLK1 transfection in PLK1 shRNA transfected PANC-1 cells recures Gemcitabine sensitivity by inhibiting ERK1/2-dependent Bim and AKT1-dependent Noxa expression in vitro. Enhanced PLK1 reduces Gemcitabinecitabine sensitivity in BxPC-3 cells by inhibiting Gemcitabine-induced Bim and Noxa expression. BI2536 (a PLK1 kinase inhibitor) treatment recures the Gemcitabine sensitivity in the PLK -transfected BxPC-3 cells by upregulation of Bim and Noxa expression in vitro. The combination of onvansertib and Gemcitabine showed significant anti-tumor effect in vivo. Mechanistically, combined treatment inhibits ERK1/2 and AKT1, and increases Bim and Noxa expression. Targeting PLK1 sensitizes PDAC cells to gemcitabine in vitro and in vivo. This indicates that combination therapy with PLK1 inhibitor may overcome gemcitabine resistance, offering a promising new therapeutic option for the treatment of gemcitabine-resistant human pancreatic cancer.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"508"},"PeriodicalIF":3.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12496299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of APT20TTMG, a modulator of the U1 snRNP complex, in glioblastoma models.","authors":"Caio Bruno Quinta de Souza Leal, Camila Guimarães Moreira Zimmer, Vanessa de Vasconcelos Castilho Sinatti, Ericks Sousa Soares, Michael S Rafii, Rafael Mantovani Bottos","doi":"10.1007/s12032-025-03057-w","DOIUrl":"https://doi.org/10.1007/s12032-025-03057-w","url":null,"abstract":"<p><p>The U1 small nuclear ribonucleoprotein (snRNP) complex is essential for pre-mRNA splicing and inhibition of premature polyadenylation. Its dysfunction has been implicated in various cancers, including glioblastoma, driving oncogenic splicing and tumor progression. This study explored the potential of APT20TTMG, a synthetic cDNA that modulates U1 snRNP misassembly, in glioblastoma. The internalization of APT20TTMG was assessed in U-87 MG cells, as well as its effects on cell viability, proliferation, and apoptosis. Athymic mice were used to evaluate the effects of intravenous APT20TTMG administration on tumor-related parameters. APT20TTMG exhibited over 50% internalization, exerting cytotoxic, cytostatic, and pro-apoptotic effects in vitro. A 22-day treatment with APT20TTMG reduced tumor volume, slowed tumor growth, and showed a trend toward increased body weight. Treatment also decreased oncogenic pathways and tended to enhance histopathological outcomes. A pilot study combining APT20TTMG with temozolomide further improved antitumor efficacy. Our results demonstrate that APT20TTMG has strong potential in correcting U1 snRNP complex dysfunction, supporting its further investigation as a strategy to modulate splicing in glioblastoma.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"507"},"PeriodicalIF":3.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the role of Cathepsin S in mitochondrial energy metabolism: implications for cancer progression and therapeutic targeting.","authors":"Rudra Prasad Adhikari, Niladry Sekhar Ghosh","doi":"10.1007/s12032-025-03065-w","DOIUrl":"https://doi.org/10.1007/s12032-025-03065-w","url":null,"abstract":"<p><p>Cathepsin S (CTSS) is a lysosomal cysteine protease traditionally recognized for its roles in protein degradation and immune responses, but emerging evidence highlights its critical involvement in cancer progression through the regulation of mitochondrial energy metabolism, tumor microenvironment modulation, and apoptosis. CTSS regulates mitochondrial calcium uptake by controlling the mitochondrial calcium uniporter (MCU), thus maintaining mitochondrial membrane potential and oxidative phosphorylation (OXPHOS). Inhibition of CTSS leads to mitochondrial calcium overload, increased reactive oxygen species (ROS) generation, impaired autophagy, and apoptosis, as demonstrated particularly in glioblastoma models. Additionally, CTSS promotes cancer progression by degrading extracellular matrix components, stimulating angiogenesis, and facilitating invasion and metastasis. Selective CTSS inhibitors enhance chemotherapy sensitivity and reduce tumor growth in various preclinical cancer models, including both glycolytic and OXPHOS-dependent tumors. However, most data originate from preclinical studies, limiting immediate clinical applicability. Moreover, CTSS inhibition may elevate ROS levels, posing potential harm to normal cells, and the complex tumor microenvironment presents challenges for targeted therapies. Overall, CTSS is a pivotal regulator that integrates mitochondrial function with tumor microenvironment dynamics, making it a promising therapeutic target. It represents a compelling target for future precision oncology strategies, offering dual benefits of direct tumor suppression and improved sensitivity to existing therapies. Nevertheless, further mechanistic studies and clinical validation are required to fully exploit CTSS's potential in cancer treatment, including deeper investigation into the molecular events linking CTSS inhibition to changes in autophagy, mitochondrial biogenesis, and metabolic reprogramming across diverse cancer subtypes.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"505"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triple-negative breast cancer: challenges, advances, and promising therapeutic interventions.","authors":"Deepanshi Sood, Charanjit Kaur, Naresh Kumar, Rajesh Kumar, Gurvinder Singh","doi":"10.1007/s12032-025-03066-9","DOIUrl":"https://doi.org/10.1007/s12032-025-03066-9","url":null,"abstract":"<p><p>Triple-Negative breast cancer (TNBC) is the most aggressive subtype of breast cancer (BC), characterized by absence of estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2). Approximately, 10-15% of BC patients are diagnosed with triple-negative breast cancer. In this review, we have summarized the approaches used for the treatment of triple-negative breast cancer. Due to the complex genetic makeup, Triple-Negative breast cancer has high potential for metastasis and is inherently difficult to treat and poses a grave threat. This review analyzes and provides insight into advancements in treatment methods and diagnostic techniques for TNBC. Schiff base compounds, capable of inducing apoptosis in malignant cells, are effective dual inhibitors of histone deacetylase type II and topoisomerase I. Detection strategies like advanced imaging techniques like core biopsy and automated breast ultrasound are important for enhancing TNBC diagnosis and treatment. The progress in developing combination therapies and improving drug delivery mechanisms has to be maintained in order to tackle the challenges in treatment. This work emphasizes the need for teamwork in the development of therapeutic approaches, which may offer new possibilities in the treatment of TNBC.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"506"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal transfer of miR-223-3p from carcinoma-associated fibroblasts promotes the malignant properties and chemoresistance of colon cancer cells by targeting NF2/Hippo signaling.","authors":"Jiaqi Zhao, Jiarui Zhang, Jing Liu, Likun Zan","doi":"10.1007/s12032-025-03063-y","DOIUrl":"https://doi.org/10.1007/s12032-025-03063-y","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) play a key role in malignant progression and chemoresistance of cancer. Accumulating studies indicate that exosomal transfer of microRNAs from CAFs to cancer cells is responsible for the effects of CAFs in cancer (Wang et al. in Cancers, 2021, https://doi.org/10.3390/cancers13133160 ). In the present study, we explored the impact of CAFs-derived exosomes on tumorigenesis and chemoresistance of colon cancer, and potential microRNAs involved in this process. CAFs were isolated form colon cancer samples. CAFs-derived exosomes were separated by ultracentrifugation. Differentially expressed microRNAs were identified by microRNA expression array. The function of CAFs-derived exsomes and exosomal microRNAs were evaluated by cell viability assay, soft agar assay, transwell invasion assay, sphere formation assay, qRT-PCR, tumor xenograft model, flow cytometry, western blot, luciferase reporter assay, biotin microRNA pull-down assay. In our study, CAFs-derived exosomes promoted proliferation, anchorage-independent growth, invasion, stemness, tumor xenograft growth and 5-FU resistance of colon cancer cells. MiR-223-3p was significantly upregulated in CAFs-derived exosomes and serum or tissue samples of colon cancer patients. Exosomal transfer of miR-223-3p facilitated malignant properties and 5-FU resistance of colon cancer cells. Moreover, NF2 was identified as a downstream target for miR-223-3p. Restored NF2 expression partially abrogated the effects caused by exosomal transfer of miR-223-3p in colon cancer cells. In addition, exosomal miR-223-3 regulated Hippo pathway in colon cancer cells by targeting NF2. Our results indicated that exosomal transfer of miR-223-3p from CAFs to colon cancer cells promoted malignant properties and chemoresistance through NF2/Hippo pathway.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"503"},"PeriodicalIF":3.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long noncoding RNA RHPN1-AS1 promotes hepatocellular carcinoma progression under hypoxia through interaction with RPS15A protein.","authors":"Qin Peng, Yu-Ting Cai, Qi Ding, Xiang-Yun Qian, Cong Xu, Hang-Cheng Zhou, Hao Chen, Heng Li, Wei Wang","doi":"10.1007/s12032-025-03049-w","DOIUrl":"https://doi.org/10.1007/s12032-025-03049-w","url":null,"abstract":"<p><p>Hypoxic microenvironment is a hallmark feature of hepatocellular carcinoma (HCC) and contributes to cancer progression. RHPN1-AS1, a long noncoding RNA (lncRNA), plays an important role in multiple cancers. However, its expression and oncogenic function under hypoxic conditions have not yet been determined. In this study, we investigated the expression changes of RHPN1-AS1 in HCC cells upon hypoxia. The effects of RHPN1-AS1 knockdown and overexpression on hypoxic HCC cells were explored. The protein partner involved in RHPN1-AS1 action in hypoxic HCC cells was characterized. We found that exposure to hypoxia led to an increase in the RHPN1-AS1 level in HCC cells, which was blocked by depletion of HIF-1α. Chromatin immunoprecipitation assay revealed the enrichment of HIF-1α at the promoter of RHPN1-AS1 in hypoxic HCC cells. Knockdown of RHPN1-AS1 suppressed HCC cell proliferation, colony formation, and invasion under hypoxia, whereas overexpression of RHPN1-AS1 promoted the proliferation and invasion of hypoxic HCC cells. Mechanistically, RHPN1-AS1 interacted with and stabilized RPS15A protein in hypoxic HCC cells. Elevated expression of RPS15A protein enhanced the proliferation and invasion of hypoxic HCC cells through activation of β-catenin signaling. Silencing of RPS15A attenuated RHPN1-AS1-induced aggressiveness and β-catenin activation in hypoxic HCC cells. In vivo tumorigenic studies confirmed that RPS15A depletion significantly reduced the growth of RHPN1-AS1-overexpressing HCC xenograft tumors. RHPN1-AS1 serves as a hypoxia-responsive lncRNA and interacts with the RPS15A protein partner to activate the β-catenin pathway, consequently enhancing HCC progression under hypoxia.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"502"},"PeriodicalIF":3.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA LOXL1-AS1 promotes ovarian cancer progression by enhanced BRIP1 mRNA stability.","authors":"Su Wan, Chang Su, Jin Ding, Ji Liu, Lingli He, Lifen Liu, Qi Peng, Guantai Ni, Weipei Zhu","doi":"10.1007/s12032-025-03055-y","DOIUrl":"https://doi.org/10.1007/s12032-025-03055-y","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) have crucial effects on the development of malignant tumors. This work focused on determining how LOXL1-AS1 contributed to epithelial ovarian cancer development. As indicated by quantitative RT-polymerase chain reaction (qRT-PCR), LOXL1-AS1 showed significant overexpression within ovarian epithelial cancer tissues and ovarian cancer cells compared with non-cancer samples and regular human epithelial cell lines. According to CCK-8, flow cytometry, plate cloning, cell scratch test, a series of cell function tests in vitro, a nude mouse transplanted tumor model, and Western blot assays, LOXL1-AS1 siRNA transfection suppressed the growth, invasion, and epithelial-to-mesenchymal transformation characteristics of SKOV3 and A2780 cells in vitro and vivo. As discovered, LOXL1-AS1 targets BRCA1-interacting protein C-terminal helicase 1 (BRIP1) mRNA, resulting in a malignant phenotype of ovarian cancer. Overexpression of BRIP1 reversed the inhibition of cell progression induced by LOXL1-AS1 siRNA. In addition, based on RNA stability experiments, LOXL1-AS1 enhanced ovarian cancer cell growth and metastasis by stabilizing BRIP1 mRNA. Our findings reveal a novel mechanism of how LOXL1-AS1 enhances epithelial ovarian cancer progression by specifically regulating BRIP1 mRNA stability. This provides the potential therapeutic application of LOXL1-AS1 targeting BRIP1 for treating ovarian cancer.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"504"},"PeriodicalIF":3.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-drives reversible cell cycle arrest in lung cancer cells via modulation of cellular redox and gene expression.","authors":"Dharmendra Kumar Maurya, Varshita Mehta, Babita Singh","doi":"10.1007/s12032-025-03058-9","DOIUrl":"10.1007/s12032-025-03058-9","url":null,"abstract":"<p><p>Hypoxia is a well-recognized clinical feature of solid tumors, including lung cancer, and is associated with poor prognosis due to its role in promoting resistance to chemotherapy and radiotherapy. To investigate the cellular consequences of hypoxia, we cultured A549 lung adenocarcinoma cells under 1% O₂ and examined their growth, cell cycle distribution, and redox status. Hypoxia significantly reduces cell proliferation and induced G1 phase cell cycle arrest, suggesting a cytostatic effect. Biochemical analysis showed a 2.64- and 2.04-fold increase in total and mitochondrial reactive oxygen species (ROS) levels, respectively, along with an elevated total thiol levels under hypoxic conditions compared to normoxia. To assess the reversibility of the hypoxic response, we performed a reciprocal oxygen exposure experiment where cells initially grown under hypoxia were re-exposed to normoxia, and vice versa. To explore the underlying molecular mechanism, we analyzed transcriptomic datasets (GEO accession: GSE48134 and GSE42416) which revealed that hypoxia downregulated key genes involved in energy metabolism (e.g., PDK4, G6PD), cell cycle progression (e.g., CCND1, CDK2), and redox regulation (e.g., GCLM, TXNRD1, NQO1, GCLC). Further, few of redox-related genes were validated by RT-PCR in A549 cells cultured under hypoxia and normoxia for 24 h. Importantly, cyclic hypoxia (intermittent hypoxia-reoxygenation) conditions showed partial restoration of some of these transcripts, supporting the transient nature of hypoxic stress, consistent with our in vitro observations. Furthermore, transcriptome profiles from adenocarcinoma patients (GEO accession: GSE30979) also match our cell line observations. Thus, our results clearly show that hypoxia causes a temporary cell cycle arrest in lung cancer cells, which is reversible when oxygen is restored.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"501"},"PeriodicalIF":3.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}