Journal of Ovarian Research最新文献

{"title":"Identification of parthanatos-related molecular subtypes and development of prognostic risk models in ovarian cancer based on multi-omics analysis.","authors":"Xiaoying Qi, Changqing Jiang, Ning Wang, Yi Han, Tingting Liu, Liying Huang, Guangjie Yin","doi":"10.1186/s13048-025-01726-y","DOIUrl":"10.1186/s13048-025-01726-y","url":null,"abstract":"<p><p>Ovarian cancer (OC) remains the most lethal gynecologic malignancy due to late-stage diagnosis, high recurrence rates, and chemoresistance. Parthanatos, a distinct caspase-independent form of programmed cell death mediated by poly (ADP-ribose) (PAR), plays a critical role in DNA damage response and tumor progression. In this study, we identified parthanatos-related genes (PRG) associated with OC prognosis based on integrated analyses of TCGA and GEO datasets, and developed a PRG-based risk model with significant prognostic value. Immune infiltration analysis and single-cell RNA sequencing revealed that high-risk patients exhibited a more immunosuppressive tumor microenvironment. Drug sensitivity profiling and clinical subgroup analyses further supported the model's clinical applicability. Among the screened PRG, TGFBI was selected for experimental validation, and in vitro assays including qRT-PCR, western blotting, colony formation, and Transwell migration demonstrated its role in promoting OC cell proliferation, invasion, and clonogenicity. These findings underscore the prognostic and biological significance of parthanatos in OC and suggest that targeting key PRG such as TGFBI may offer novel therapeutic strategies to improve patient outcomes.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"137"},"PeriodicalIF":3.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12217911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553791","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":"Methylated ARHGAP40 DNA as a potential biomarker for early diagnosis in high-grade ovarian serous cancer.","authors":"Jiaxin Chai, Dongni Leng, Shuwei Guo, Rusong Zhang, Jiandong Wang, Yun Gu, Qiu Rao","doi":"10.1186/s13048-025-01729-9","DOIUrl":"10.1186/s13048-025-01729-9","url":null,"abstract":"<p><p>Ovarian cancer ranks as the eighth most common malignancy in women globally. Early detection remains a critical challenge for improving ovarian cancer diagnosis and treatment outcomes. Our prior study demonstrated that ARHGAP40 downregulation in basal cell carcinoma is attributed to CpG island hypermethylation. However, the expression and methylation status of ARHGAP40 in ovarian cancer remain unexplored. Here, we investigated ARHGAP40 protein expression in normal fallopian tubes, ovarian benign tumors, borderline tumors, low-grade serous carcinoma (LGSC) and high-grade serous carcinomas (HGSC). Methylation analysis of the ARHGAP40 was performed using bisulfite sequencing PCR (BSP). MethyLight assays were developed to detect methylated circulating tumor DNA (ctDNA) fragments of ARHGAP40. IHC results revealed absent or weak ARHGAP40 protein expression in 93.8% (30/32) of HGSC, 11.1% (2/18) of borderline tumors, and in 14.3% (1/7) of LGSC cases. ARHGAP40 protein expression was robust expressed in all normal fallopian tubes (15/15) and benign ovarian tumors (8/8). CpG island hypermethylation in the ARHGAP40 promoter showed a strong inverse correlation with protein expression (P < 0.001). Furthermore, methylated ctDNA for ARHGAP40 was detected in 80.0% (4/5) of HGSC patients' plasma, but not in benign tumor (0/3) and healthy controls (0/15). Our findings suggest that promoter hypermethylation may be a mechanism underlying ARHGAP40 silencing in HGSC. Detection of methylated ARHGAP40 ctDNA may serve as a noninvasive biomarker for early diagnosis and monitoring of HGSC. While our findings suggest the potential of methylated ARHGAP40 as an early diagnostic biomarker, the small sample size warrants validation in larger cohorts.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"140"},"PeriodicalIF":3.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553792","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":"Laser-assisted hatching is associated with reduced re-expansion of vitrified-thawed blastocysts and has no significant effect on embryo implantation.","authors":"Shutian Jiang, Xueyi Jiang, Yan Mi, Xue Sun, Qifeng Lyu, Wenzhi Li","doi":"10.1186/s13048-025-01723-1","DOIUrl":"10.1186/s13048-025-01723-1","url":null,"abstract":"<p><strong>Background: </strong>Studies have shown that vitrified-thawed blastocyst re-expansion capacity is a good predictor of implantation. However, whether assisted hatching (AH) influences re-expansion is currently unstudied. Also, whether AH improves subsequent implantation rate remains highly uncertain.</p><p><strong>Objectives: </strong>To investigate the impact of AH on re-expansion and subsequent implantation in vitrified-thawed blastocysts transfer cycles.</p><p><strong>Method: </strong>The absolute initial single vitrified-thawed blastocyst cycles of patients between August 2019 and April 2024 in our center were included in this retrospective cohort study, totaling 4637 cycles. Grouping was performed according to laser-AH or not. Stratified analyses according to different trophoblastic ectoderm (TE) grades were applied (TE were categorized into three different grades (A-C) according to their number and cohesiveness), with specific focus on blastocysts with TE grade of C. Subgroup analyses were then carried out based on blastocyst stage (Day5 or Day6), in which AH and Non-AH were compared separately. Multifactorial regression analyses were performed on the main outcomes to clarify the effect of laser-AH.</p><p><strong>Results: </strong>There were no differences in pregnancy outcomes between AH group and Non-AH group, though the blastocyst stage proportions differed. Subgroup analysis based on blastocyst stage still revealed no statistically significant differences in pregnancy outcomes regarding AH or not (both in Day5 and Day6 blastocysts); while AH group had a lower re-expansion rate than Non-AH group in Day6 blastocysts (78.9% vs. 84.0%, P = 0.006). Multifactorial regression showed that AH had no effect on biochemical pregnancy rate in all cycles (aOR: 1.064, 95% CI: 0.938-1.206, P = 0.337), but increased the probability of implantation in TE grade = C cycles (aOR: 1.340, 95% CI: 1.017-1.766, P = 0.038). In the binary regression analysis on re-expansion rate, AH presented a negative effect both in all cycles and in TE grade = C cycles (all cycles: aOR: 0.774, 95% CI: 0.646-0.827, P = 0.005; TE = C cycles: aOR: 0.688, 95% CI: 0.481-0.984, P = 0.040).</p><p><strong>Conclusion: </strong>Laser-AH negatively affects the ability of vitrified-thawed blastocysts to re-expand. Laser-AH had no significant effect on implantation in all blastocysts. AH may only be beneficial for the implantation of blastocysts with TE grade C.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"136"},"PeriodicalIF":3.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340217","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":"Transcriptomic analysis of theca cells in a PCOS rat model: insights into follicular development.","authors":"Chen Yuanyuan, Sun Ningyu, Lu Lu, Zhang Wuwen, Li Kai, Li Yanting, He Junlan, Cheng Xiang, Zhou Jing, Yan Hua, Yin Ping","doi":"10.1186/s13048-025-01663-w","DOIUrl":"10.1186/s13048-025-01663-w","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to analyze differentially expressed genes in theca cells of polycystic ovary syndrome (PCOS) rats using transcriptomic sequencing. Bioinformatics analysis and PCR validation were performed to identify genes involved in follicular development regulation in PCOS.</p><p><strong>Methods: </strong>Twenty 6-week-old female SD rats with regular estrous cycles were divided into two groups (PCOS and control, n = 10 each). The PCOS model was induced with a 1.0 mg·kg⁻¹ Letrozole solution. Theca cells were collected for transcriptomic sequencing, and differentially expressed genes were analyzed. Functional annotations and pathway enrichment were determined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Gene interaction network and hub gene analyses were conducted, followed by RT-qPCR validation.</p><p><strong>Results: </strong>PCOS rats exhibited increased body weight and irregular estrous cycles. A total of 1,114 differentially expressed genes were identified, including 516 upregulated and 598 downregulated genes. Fifty hub genes were selected for further analysis. GO and KEGG pathway enrichment analysis revealed significant involvement of the MAPK and PI3K-Akt signaling pathways. PCR validation confirmed that Cyp17a1, Cyp11a1, S6k1, mTOR, Akt, Kit, and Tek were significantly upregulated in the PCOS group (P < 0.05).</p><p><strong>Conclusion: </strong>Transcriptomic analysis identified key genes and pathways involved in follicular development dysregulation in PCOS rats, providing potential targets for further research.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"135"},"PeriodicalIF":3.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340218","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":"Ovarian remodeling and aging-related chronic inflammation and fibrosis in the mammalian ovary.","authors":"Yuanyuan Zhu, Heming Sun, Ting Gao, Shengdi Hou, Yuebo Li, Ying Xu, Qingxia Zhang, Dingqing Feng","doi":"10.1186/s13048-025-01715-1","DOIUrl":"10.1186/s13048-025-01715-1","url":null,"abstract":"<p><strong>Background: </strong>The female ovary undergoes constant follicular atresia from birth, as well as ovulation and corpus luteum (CL) regression during reproductive age, leading to recurrent ovarian remodeling and ultimately resulting in ovarian aging. However, aging-related cellular and molecular changes in the ovary remain poorly explored.</p><p><strong>Results: </strong>Using ovarian transcriptomics, we characterized the changes in gene expression in the ovaries of young (2-month-old), middle-aged (6-month-old) and old (12-month-old) mice. Our analyses revealed that the stromal cell markers THY1 and CD44 were significantly upregulated, whereas the markers of oocytes, granulosa cells and theca cells were markedly downregulated in old mice; thus, endocrine dysfunction occurred. We also found that MAPK pathway- and inflammation response-related genes were enriched and that the populations of Tregs, macrophages and NK cells notably decreased in aged ovaries, which was confirmed by flow cytometry. However, during superovulation, the proportions of macrophages and NK cells steadily increased as the follicles developed and ovulated, whereas the proportion of macrophages sharply decreased after ovulation. We further verified these ovarian changes in specific cell markers and rate-limiting enzymes for steroid hormone synthesis by immunohistochemistry (IHC) and collagen deposition by Masson's trichrome staining in pre- and postmenopausal women.</p><p><strong>Conclusions: </strong>These results from clinical samples demonstrated that aging-associated changes were similar to those observed in mice and were strongly correlated with the age of the woman. Therefore, this report provides critical insights into aging-related cellular and molecular changes in the ovary.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"133"},"PeriodicalIF":3.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325996","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":"The risk factors, pathogenesis and treatment of premature ovarian insufficiency.","authors":"Yanjing Huang, Zhuo Liu, Yuli Geng, Fan Li, Runan Hu, Yufan Song, Mingmin Zhang, Kunkun Song","doi":"10.1186/s13048-025-01714-2","DOIUrl":"10.1186/s13048-025-01714-2","url":null,"abstract":"<p><p>Premature ovarian insufficiency (POI) is a prevalent condition that impacts female reproductive health and overall well-being. It is characterized by ovarian dysfunction, estrogen deficiency, and increased gonadotropin levels in women under 40 years old. The exact etiology and pathogenesis of POI remain incompletely understood, posing significant challenges for its treatment and prevention. This review article examines the pathogenic factors and mechanisms involved in POI, with a particular focus on the impact of environmental toxicants such as atmospheric particulate matter, endocrine-disrupting chemicals, pesticides, microplastics, heavy metals, and cigarette smoke on the development of POI. Furthermore, the treatments for POI are outlined, encompassing hormone replacement therapy, stem cell and exosome therapy, melatonin therapy, traditional Chinese medicine, in vitro activation, platelet-rich plasma therapy, and ovarian tissue cryopreservation. The primary objective is to raise awareness about the potential detrimental effects of environmental toxicant exposure on ovarian function and reserve, urging individuals to minimize their exposure to harmful substances and advocate for environmental protection. This review also aims to serve as a valuable resource for the prevention and management of POI.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"134"},"PeriodicalIF":3.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325997","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":"Retraction Note: High levels of fatty acid-binding protein 5 excessively enhances fatty acid synthesis and proliferation of granulosa cells in polycystic ovary syndrome.","authors":"Jingyu Liu, Jie Li, Xin Wu, Mei Zhang, Guijun Yan, Haixiang Sun, Dong Li","doi":"10.1186/s13048-025-01713-3","DOIUrl":"10.1186/s13048-025-01713-3","url":null,"abstract":"","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"132"},"PeriodicalIF":3.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310076","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":"Phthalates unleashed: decoding ovarian carcinogenesis through multi-omics networks, single-cell insights, and molecular docking.","authors":"Junchan Yang, Min Luo, Hongjun Wang, Jinfa Huang","doi":"10.1186/s13048-025-01710-6","DOIUrl":"10.1186/s13048-025-01710-6","url":null,"abstract":"<p><strong>Background: </strong>Despite epidemiological studies linking phthalates to ovarian cancer, their multi-target molecular mechanisms remain unresolved, hindering biomarker discovery and preventive strategies. This study integrates network toxicology, multi-omics analyses, and molecular docking to systematically delineate phthalate-driven oncogenic pathways, thereby bridging mechanistic gaps and informing targeted interventions.</p><p><strong>Results: </strong>We identified 234 potential targets related to phthalate exposure and ovarian cancer. Enrichment analysis revealed that these genes are associated with HIF-1 signaling, and metabolic pathways that promote cancer progression. Seven core genes were identified, with six (GAPDH, CASP3, PPARG, ESR1, CYCS, SIRT1, and CCND1) exhibiting differential expression in the TCGA ovarian cancer cohort. Single-cell analysis confirmed their widespread expression across various cell types, underscoring their roles in tumor biology. Molecular docking revealed specific binding interactions between phthalates and six core proteins.</p><p><strong>Conclusions: </strong>Integrated computational analyses indicate that phthalates (DEP, DMP, DOP) may drive ovarian carcinogenesis through metabolic reprogramming (HIF-1α/glycolysis), strong binding to SIRT1/PPARα regulators, and tumor microenvironment remodeling. These findings establish a framework for prioritizing environmental carcinogens and identifying exposure biomarkers, with implications for reevaluating phthalate safety and elucidating the SIRT1-HIF1-PPARα axis in cancer pathogenesis.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"131"},"PeriodicalIF":3.8,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293950","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":"Fatty acid metabolism of granulose cells and follicular fluid and their associations with embryo quality in normal-weight women with PCOS.","authors":"Ye Tian, Aiyuan Wang, Fang Li, Siyu Wang, Jie Shang, Kai Zhang, Xiaohong Bai","doi":"10.1186/s13048-025-01711-5","DOIUrl":"10.1186/s13048-025-01711-5","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder in women of reproductive age. The granulosa cell metabolism correlated with oocyte competence. However, the alteration of fatty acid in granulosa cell of PCOS patients is unclear. Besides, obesity per se is related to dysfunction of oocyte quality. Hence, this study was aimed to comprehensively investigate the fatty acid alteration of oocyte environment and their associations with embryo quality in normal weight women with PCOS.</p><p><strong>Method: </strong>Two independent prospective cohorts included women with PCOS and age-BMI-matched controls that underwent IVF treatment were recruited. DIA-mass spectrometry-based proteomics analysis and absolute quantification of fatty acids were conducted in granulosa cells and follicular fluid from women with PCOS and controls, and then the relationship between fatty acid level and embryo quality in PCOS patients was analysed.</p><p><strong>Results: </strong>Proteomic analysis in cohort 1 revealed 205 differentially expressed proteins in the granulosa cells of normal-weight PCOS patients compared with those of controls. Functional enrichment analysis and metabolism score calculation revealed that fatty acid metabolism pathways, especially the biosynthesis of unsaturated fatty acids, were downregulated. The hallmark fatty acid metabolism score was negatively correlated with the total testosterone level and the AMH level (R=-0.52, P = 0.004; R=-0.64, P = 0.00017, respectively).Compared with those in the control group, the levels of the SFAs myristic acid (C14:0) and MUFAs nervonic acid (C24:1) in the follicular fluid of PCOS patients in cohort 1 were greater, whereas the ratio of PUFAs LA: ALA was lower, which were validated by cohort 2. C14:0 was moderately positively correlated with the basal LH level and LH/FSH ratio, even after correction for multiple comparisons. Receiver operating characteristic (ROC) analysis combining the C24:1, C14:0, and LA: ALA ratios with the seven fatty acid metabolic-related proteins revealed that the predictive accuracy for PCOS was 0.86.</p><p><strong>Conclusion: </strong>In normal-weight women with PCOS, fatty acid disturbance occurs in granulosa cells and follicular fluid, and also suggesting a role for C14:0, C24:1 and LA: ALA in PCOS patients, independent of obesity.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"130"},"PeriodicalIF":3.8,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293949","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":"Hyptolide induces ER stress-mediated cell death and enhances GSK3β-regulated cisplatin chemosensitivity in ovarian cancer.","authors":"Yusi Luluk Rahmania, Person Pesona Renta, Damar Nurwahyu Bima, Yu-Shan Lin, Ngoc Thang Nguyen, Pin-Yu Wang, Meiny Suzery, Wen-Tai Chiu","doi":"10.1186/s13048-025-01712-4","DOIUrl":"10.1186/s13048-025-01712-4","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer is a highly prevalent cancer among women with a high risk for relapse and drug resistance. Seventy eight percent of women diagnosed with ovarian cancer live for at least one year after diagnosis. Hyptolide, a natural compound, has been shown to act as an anti-inflammatory and antibacterial agent, and latest research shows that it acts as an anticancer agent. These properties indicate that hyptolide may be a potential treatment option for ovarian cancer, including chemoresistant cases; however, its effects in chemoresistant ovarian cancer have not yet been demonstrated, and the mechanisms underlying its induction of cell death remain unclear.</p><p><strong>Results: </strong>We found that hyptolide inhibited cell viability in ovarian cancer cell lines, regardless of their chemoresistance, and these effects were mediated by ER stress and the activation of GRP78 and ATF6. Combined treatment of cisplatin-resistant cell lines with hyptolide and cisplatin demonstrated a synergistic effect, enhancing apoptosis. Additionally, the reversal of chemoresistance with hyptolide treatment was mediated by β-catenin cytoplasm translocation leading to E-cadherin expression, ultimately promoting mesenchymal-epithelial transition.</p><p><strong>Conclusion: </strong>Our findings suggest that hyptolide induces ER stress-mediated cell death and overcomes cisplatin chemoresistance in ovarian cancer cells, supporting its potential use as a chemotherapeutic agent.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"129"},"PeriodicalIF":3.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284970","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}