International journal of oncology最新文献

{"title":"Emodin inhibits benzidine‑enhanced survival and migration of upper urinary tract urothelial carcinoma cells by targeting the PKA/COX2 signaling pathway.","authors":"Yanyang Jin, Chengcai Wang, Kun Feng, Xiaowei Wang, Ming Tong, Guangquan Tong","doi":"10.3892/ijo.2024.5691","DOIUrl":"10.3892/ijo.2024.5691","url":null,"abstract":"<p><p>The carcinogenic effects of benzidine (BZ) on bladder cancer are well documented, but its potential for promoting upper urinary tract urothelial carcinoma (UTUC) remains unclear. The ability of emodin, a natural pharmaceutical compound, to prevent BZ‑associated UTUC has not been previously explored. To the best of our knowledge, the present study is the first to reveal that BZ significantly enhanced the survival and migration of UTUC cell lines <i>in vitro</i>. Furthermore, <i>in vivo</i> experiments demonstrated that BZ promoted an increase in the size of subcutaneous tumors in nude mice. Further investigation revealed that BZ upregulated the expression of protein kinase A (PKA) and cyclooxygenase 2 (COX2), along with downstream matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF), in UTUC cells. Moreover, BZ increased the levels of cyclic adenosine monophosphate (cAMP) and prostaglandin E2 (PGE2) in cell lysates. By contrast, emodin reduced the PKA and COX2 expression levels compared with the BZ‑treated group. Similarly, the <i>in vivo</i> experiments demonstrated that emodin significantly inhibited tumor growth in BZ‑pretreated nude mice, accompanied by reductions in the cAMP, PGE2, MMP9 and VEGF levels. These findings elucidated the role of BZ in promoting UTUC progression. Additionally, emodin has emerged as a novel inhibitor of BZ‑induced UTUC development through PKA/COX2 inhibition, suggesting its potential as a natural therapeutic agent against BZ‑associated UTUC.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"65 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11419409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PPM1G and its diagnostic, prognostic and therapeutic potential in HCC (Review).","authors":"Xiaomin Zhang, Heyue Wang, Yiran Yuan, Jieya Zhang, Jize Yang, Lei Zhang, Jiefeng He","doi":"10.3892/ijo.2024.5697","DOIUrl":"10.3892/ijo.2024.5697","url":null,"abstract":"<p><p>Global statistics indicate that hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer‑related death. Protein phosphatase Mg²⁺/Mn²⁺ dependent 1G (PPM1G, also termed PP2Cγ) is one of the 17 members of the PPM family. The enzymatic activity of PPM1G is highly reliant on Mg²⁺ or Mn²⁺ and serves as a dephosphorylation regulator for numerous key proteins. PPM1G, functioning as a phosphatase, is involved in a number of significant biological processes such as the regulation of eukaryotic gene expression, DNA damage response, cell cycle and apoptosis, cell migration ability, cell survival and embryonic nervous system development. Additionally, PPM1G serves a role in regulating various signaling pathways. In recent years, further research has increasingly highlighted <i>PPM1G</i> as an oncogene in HCC. A high expression level of PPM1G is closely associated with the occurrence, progression and poor prognosis of HCC, offering notable diagnostic and therapeutic value for this patient population. In the present review, the regulatory role of PPM1G in diverse biological processes and signaling pathway activation in eukaryotes is evaluated. Furthermore, its potential application as a biomarker in the diagnosis and prognosis evaluation of HCC is assessed, and future prospects for HCC treatment strategies centered on PPM1G are discussed.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"65 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZNF740 facilitates the malignant progression of hepatocellular carcinoma via the METTL3/HIF‑1A signaling axis.","authors":"Hao Zhang, Bing Han, She Tian, Yongjun Gong, Li Liu","doi":"10.3892/ijo.2024.5693","DOIUrl":"10.3892/ijo.2024.5693","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the second leading cause of cancer‑related death, and efficient treatments to facilitate recovery and enhance long‑term outcomes are lacking. Zinc finger proteins (ZNFs), known as the largest group of transcription factors, have gained interest for their roles in HCC by stimulating the transcription of well‑known tumor‑causing genes. However, the specific roles and molecular mechanisms of ZNF740 in HCC remain unknown. The present study performed bioinformatics analysis and RNA‑sequencing analysis of differentially expressed genes in HCC, detected ZNF740 expression levels in HCC using reverse transcription‑quantitative PCR, western blotting and immunohistochemistry, and explored the effects of ZNF740 on the progression of liver cancer <i>in vitro</i> and <i>in vivo</i> using cellular functionality assays and cell‑derived xenografts. In addition, a dual‑luciferase reporter assay was performed to analyze the binding of ZNF740 with the METTL3 promoter. Furthermore, cell functionality experiments were performed to analyze whether ZNF740 promotes the proliferation of liver cancer cells in a METTL3‑dependent manner. Bioinformatics and immunoprecipitation assays were further used to analyze the molecular mechanism of ZNF740 in liver cancer. The present study demonstrated that ZNF740 expression was upregulated in HCC. Mechanistically, overexpressed ZNF740 interacted with the methyltransferase‑like 3 (METTL3) promoter and increased METTL3 expression, leading to the stabilization of hypoxia‑inducible factor‑1A (HIF1A) mRNA in an N6‑methyladenosine/YTH N6‑methyladenosine RNA‑binding protein 1‑dependent manner. Eventually, the ZNF740/METTL3/HIF1A signaling axis may facilitate the proliferation, invasion and metastasis of liver cancer via METTL3/HIF‑1A signaling. The present findings revealed the important role of ZNF740 and suggested a potential therapeutic approach that might improve clinical therapies for liver cancer.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"65 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MEF2A is a transcription factor for circPVT1 and contributes to the malignancy of acute myeloid leukemia.","authors":"Kun Wu, Yuntao Li, Bo Nie, Chong Guo, Xiaobo Ma, Linyan Li, Shenju Cheng, Yanhong Li, Shan Luo, Yun Zeng, Jian Yu, Mingxia Shi","doi":"10.3892/ijo.2024.5699","DOIUrl":"10.3892/ijo.2024.5699","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a hematological malignancy with a high relapse rate and a poor survival rate. The circular RNA circPVT1 and myocyte enhancer factor 2A (MEF2A) have unique functions in the progression of AML; however, the underlying mechanisms and clinical significance remain to be clarified. Bioinformatics and database analyses were used to assess the transcription factors and target genes of circPVT1. Dual‑luciferase reporter gene and argonaute 2‑RNA immunoprecipitation assays were used to verify the targeted relationships. The expression levels of related genes and proteins were detected by reverse transcription‑quantitative PCR and western blotting. Cell viability and apoptosis were detected by Cell Counting Kit‑8 assay and flow cytometry, respectively. The results revealed that circPVT1 was highly expressed in AML samples and cell lines, and that MEF2A regulated the expression of circPVT1. MEF2A overexpression promoted cell viability and epithelial‑mesenchymal transition (EMT), and inhibited cell apoptosis. In addition, circPVT1 was revealed to target the regulation of microRNA (miR)‑455‑3p, and miR‑455‑3p targeted the regulation of MCL1 expression, thus indicating that circPVT1 promoted MCL1 expression through its interaction with miR‑455‑3p. Furthermore, cells were transfected with the small interfering RNA‑(si)‑circPVT1, miR‑455‑3p inhibitor or si‑MCL1, and si‑circPVT1 and si‑MCL1 inhibited the viability and EMT of NB4 and HL‑60 cells. However, the miR‑455‑3p inhibitor had the opposite effect on cells. In conclusion, MEF2A may act as a transcription factor of circPVT1 to promote the malignant process of AML, and knockdown of circPVT1 could inhibit the viability and EMT of AML cells through the miR‑455‑3p/MCL1 axis.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"65 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Corrigendum] Circular RNAs in osteosarcoma: An update of recent studies (Review).","authors":"Le Zeng, Longzhou Liu, Wen-Juan Ni, Fuhua Xie, Xiao-Min Leng","doi":"10.3892/ijo.2024.5696","DOIUrl":"https://doi.org/10.3892/ijo.2024.5696","url":null,"abstract":"<p><p>Subsequently to the publication of the above review, the authors have contacted the Editorial Office to explain that the article was regrettably published containing a few errors. First, on p. 3, left‑hand column, the '<b>3. Functions of circRNAs in OS</b>' section, line 23, the sentence here should have read as follows (changes shown in bold, where appropriate): '<b>Circ_0001649</b> has been reported as <b>a sponge</b> of various miRNAs that inhibit cell proliferation (62,83).' (i.e., mentioning 'Circ_0001649' twice was an error/oversight). Secondly, in the '<b>4. Mechanisms of circRNAs in OS</b>' section, paragraph 5, line 23 on p. 8, the four consecutive sentences that start on this line should have read as follows: '<b>Hsa_circ_0000190</b> is significantly downregulated in OS tissues and cell lines. This circRNA inhibits the Wnt/β‑catenin signaling pathway by sponging miR‑767‑5p, the target of which is TET1 <b>(61)</b>. And hsa_circ_0002052 can sponge miR‑1205, the target of which is adenomatosis polyposis coli 2 (APC2), a negative regulator of the Wnt/β‑catenin signaling pathway. Hence, <b>hsa_circ_0000190 and hsa_circ_0002052</b> <b>can function</b> as inhibitors of the Wnt/β‑catenin signaling pathway by promoting TET1 and APC2 expression via miRNA sponging, ultimately resulting in the delayed development of OS <b>(50,61)</b>.' (i.e., the first sentence was corrected to read 'Hsa_circ_0000190' and 'hsa_circ_0000190' was added to the fourth sentence, and ref. 61 was added to the second sentence in this section, and included with ref. 50 at the end of the fourth sentence). Thirdly (and finally), changes were required to both Fig. 3 and its accompanying legend, and these are featured on the next page; essentially, 'CircRNA CDR1as (47)' should not have been included in the Fig. 3 legend as this circRNA is not described in the figure, and some changes have been made to the figure itself in terms of wrongly placed lines and arrows. The authors are grateful to the Editor of <i>International Journal of Oncology</i> for allowing them this opportunity to publish this Corrigendum, and all the authors agree with its publication. Furthermore, the authors apologize to the readership for any inconvenience caused. [International Journal of Oncology 63: 123, 2023; DOI: 10.3892/ijo.2023.5571].</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"65 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AUP1 transcriptionally activated by KDM5B reprograms lipid metabolism to promote the malignant progression of cervical cancer.","authors":"Yingping Zhu, Wenjuan Yang, Xinyan Wang, Mengmeng Chen","doi":"10.3892/ijo.2024.5695","DOIUrl":"10.3892/ijo.2024.5695","url":null,"abstract":"<p><p>Cervical cancer is one of the reproductive malignancies threatening women's lives worldwide. In the present study, it was aimed to explore the role and mechanism of ancient ubiquitous protein 1 (AUP1) in cervical cancer. Through bioinformatics analysis, AUP1 expression in cervical cancer tissues and the correlation between AUP1 and the prognosis of patients were analyzed. AUP1 expression in several cervical cancer cell lines was detected. Following the co‑transfection of short hairpin RNA specific to AUP1 with or without lysine demethylase 5B (KDM5B) overexpression plasmids in SiHa cells, the proliferation and apoptosis of SiHa cells were detected. Additionally, wound healing and Transwell assays were used to detect SiHa cell migration and invasion. Cellular lipid droplets level was detected using the Oil red O staining. Meantime, the levels of triglyceride, cholesterol, oxygen consumption rates and expression of lipid metabolism‑related proteins were detected to assess the lipid metabolism in SiHa cells. Then, the luciferase reporter assay and ChIP assay were used to verify the binding between KDM5B and AUP1. Finally, the effects of AUP1 and KDM5B on the growth and lipid metabolism in SiHa tumor‑bearing mice were measured. AUP1 was significantly upregulated in cervical cancer tissues and cells. AUP1 interference inhibited the malignant biological behaviors and lipid metabolism reprogramming of SiHa cells, which was blocked by KDM5B overexpression. Moreover, KDM5B could transcriptionally activate AUP1 and upregulate AUP1 expression. Furthermore, AUP1 knockdown transcriptionally regulated by KDM5B limited the tumor growth and suppressed the lipid metabolism reprogramming <i>in vivo</i>. Collectively, AUP1 could be transcriptionally activated by KDM5B to reprogram lipid metabolism, thereby promoting the progression of cervical cancer. These findings reveal possible therapeutic strategies in targeting metabolic pathways.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"65 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Retracted] Long non‑coding RNA HOTAIR modulates HLA‑G expression by absorbing miR‑148a in human cervical cancer.","authors":"Jinbao Sun, Haipeng Chu, Jianghai Ji, Gaoxiang Huo, Qinglei Song, Xue Zhang","doi":"10.3892/ijo.2024.5685","DOIUrl":"10.3892/ijo.2024.5685","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the HLA western blotting data shown for the HeLa cell line in Fig. 3D on p. 948 were strikingly similar to data appearing in different form in Fig. 3 in the following article written by different authors at different research institutes that was submitted for publication at around the same time, and for which an Expression of Concern has subsequently been published: Sun L, Xue H, Jiang C, Zhou H, Gu L, Liu Y, Xu C and Xu Q: LncRNA DQ786243 contributes to proliferation and metastasis of colorectal cancer both <i>in vitro</i> and <i>in vivo</i>. Biosci Rep 36: e00328, 2016. In addition, it was also noted that certain of the control western blotting data featured in Figs. 3D and 5B were strikingly similar, even though different experiments were being reported on in these figures.  In view of the fact that the contentious data were submitted for publication at around the same time, the Editor of <i>International Journal of Oncology</i> has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 49: 943‑952, 2016; DOI: 10.3892/ijo.2016.3589].</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"65 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGFR‑related phenotypic and functional profile of CAFs in prognostication of breast cancer (Review).","authors":"Julia Solek, Marcin Braun, Rafal Sadej, Hanna M Romanska","doi":"10.3892/ijo.2024.5682","DOIUrl":"10.3892/ijo.2024.5682","url":null,"abstract":"<p><p>While preclinical studies consistently implicate FGFR‑signalling in breast cancer (BC) progression, clinical evidence fails to support these findings. It may be that the clinical significance of FGFR ought to be analysed in the context of the stroma, activating or repressing its function. The present review aimed to provide such a context by summarizing the existing data on the prognostic and/or predictive value of selected cancer‑associated fibroblasts (CAFs)‑related factors, that either directly or indirectly may affect FGFR‑signalling. PubMed (https://pubmed.ncbi.nlm.nih.gov/) and Medline (https://www.nlm.nih.gov/medline/medline_home.html) databases were searched for the relevant literature related to the prognostic and/or predictive significance of: CAFs phenotypic markers (αSMA, S100A4/FSP‑1, PDGFR, PDPN and FAP), CAFs‑derived cognate FGFR ligands (FGF2, FGF5 and FGF17) or inducers of CAFs' paracrine activity (TGF‑β1, HDGF, PDGF, CXCL8, CCL5, CCL2, IL‑6, HH and EGF) both expressed in the tumour and circulating in the blood. A total of 68 articles were selected and thoroughly analysed. The findings consistently identified upregulation of αSMA, S100A4/FSP‑1, PDGFR, PDPN, HDGF, PDGF, CXCL8, CCL5, CCL2, IL‑6, HH and EGF as poor prognostic markers in BC, while evaluation of the prognostic value of the remaining markers varied between the studies. The data confirm an association of CAFs‑specific features with BC prognosis, suggesting that both quantitative and qualitative profiling of the stroma might be required for an assessment of the true FGFR's clinical value.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"65 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Retracted] Effects of RUNX3 mediated Notch signaling pathway on biological characteristics of colorectal cancer cells.","authors":"Hang Li, Dan Li, Ning Meng","doi":"10.3892/ijo.2024.5679","DOIUrl":"10.3892/ijo.2024.5679","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell apoptotic data shown in Fig. 5A on p. 2065, and the Transwell migration and invasion assay data shown in Fig. 6A and C on p. 2066 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to <i>International Journal of Oncology</i>, or were submitted for publication at around the same time. Given that the abovementioned data had already apparently been published previously, the Editor of <i>International Journal of Oncology</i> has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 50: 2059‑2068, 2017; DOI: 10.3892/ijo.2017.3988].</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"65 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aurantio‑obtusin regulates lipogenesis and ferroptosis of liver cancer cells through inhibiting SCD1 and sensitizing RSL3.","authors":"Wen Liu, Jun Deng, Xiao-Jun Tao, Ya Peng, Xiang-Ding Chen, Xiao-Chao Qu, Hong-Wen Deng, Li-Jun Tan","doi":"10.3892/ijo.2024.5680","DOIUrl":"10.3892/ijo.2024.5680","url":null,"abstract":"<p><p>Ferroptosis, characterized by iron‑mediated non‑apoptotic cell death and alterations in lipid redox metabolism, has emerged as a critical process implicated in various cellular functions, including cancer. Aurantio‑obtusin (AO), a bioactive compound derived from Cassiae semen (the dried mature seeds of <i>Cassie obtusifolia</i> L. or <i>Cassia toral</i> L.), has anti‑hyperlipidemic and antioxidant properties; however, to the best of our knowledge, the effect of AO on liver cancer cells remains unclear. The Cell Counting Kit‑8, EdU staining and migration assays were employed to assess the anti‑liver cancer activity of AO. Intracellular levels of glutathione peroxidase 4 protein and lipid peroxidation were measured as indicators of ferroptotic status. Immunohistochemical analyses, bioinformatics analyses and western blotting were conducted to evaluate the potential of stearoyl‑CoA desaturase 1 (SCD1) in combination with ferroptosis inducers for the personalized treatment of liver cancer. The present study revealed that AO significantly inhibited the proliferation of liver cancer cells <i>in vitro</i> and <i>in vivo</i>. Mechanistically, AO inhibited AKT/mammalian target of rapamycin (mTOR) signaling, suppressed sterol regulatory element‑binding protein 1 (SREBP1) expression, and downregulated fatty acid synthase expression, thereby inhibiting <i>de novo</i> fatty acid synthesis. Further investigations demonstrated that AO suppressed glutathione peroxidase 4 protein expression through the nuclear factor erythroid 2‑related factor 2/heme oxygenase‑1 pathway, induced ferroptosis in liver cancer cells, and simultaneously inhibited lipogenesis by suppressing SCD1 expression through the AKT/mTOR/SREBP1 pathway. Consequently, this increased the sensitivity of liver cancer cells to the ferroptosis inducer RSL3. Additionally, the enhanced effects of AO and RSL3, which resulted in significant tumor suppression, were confirmed in a xenograft mouse model. In conclusion, the present study demonstrated that AO induced ferroptosis, downregulated the expression of SCD1 and enhanced the sensitivity of liver cancer cells to the ferroptosis inducer RSL3. The synergistic use of AO and a ferroptosis inducer may have promising therapeutic effects in liver cancer cells.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"65 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}