{"title":"Ojeok-san enhances platinum sensitivity in ovarian cancer by regulating adipocyte paracrine IGF1 secretion.","authors":"Jiong Ma, Junyan Li, Xuejun Chen, Yanyan Ma","doi":"10.1080/21623945.2023.2282566","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Platinum is a commonly used drug for ovarian cancer (OvCa) treatment, but drug resistance limits its clinical application. This study intended to delineate the effects of adipocytes on platinum resistance in OvCa.</p><p><strong>Methods: </strong>OvCa cells were maintained in the adipocyte-conditioned medium. Cell viability and apoptosis were detected by CCK-8 and flow cytometry, separately. Proliferation and apoptosis-related protein expression were assayed by western blot. The IC<sub>50</sub> values of cisplatin and carboplatin were determined using CCK-8. IGF1 secretion and expression were assayed via ELISA and western blot, respectively. A xenograft model was established, and pathological changes were detected by H&E staining. Proliferation and apoptosis-associated protein expression was assessed via IHC.</p><p><strong>Results: </strong>Adipocytes promoted the viability and repressed cell apoptosis in OvCa, as well as enhancing platinum resistance, while the addition of IGF-1 R inhibitor reversed the effects of adipocytes on proliferation, apoptosis, and drug resistance of OvCa cells. Treatment with different concentrations of Ojeok-san (OJS) inhibited the adipocyte-induced platinum resistance in OvCa cells by suppressing IGF1. The combined treatment of OJS and cisplatin significantly inhibited tumour growth <i>in vivo</i> with good mouse tolerance.</p><p><strong>Conclusion: </strong>In summary, OJS inhibited OvCa proliferation and platinum resistance by suppressing adipocyte paracrine IGF1 secretion.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761029/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Adipocyte","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/21623945.2023.2282566","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/11/22 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Platinum is a commonly used drug for ovarian cancer (OvCa) treatment, but drug resistance limits its clinical application. This study intended to delineate the effects of adipocytes on platinum resistance in OvCa.
Methods: OvCa cells were maintained in the adipocyte-conditioned medium. Cell viability and apoptosis were detected by CCK-8 and flow cytometry, separately. Proliferation and apoptosis-related protein expression were assayed by western blot. The IC50 values of cisplatin and carboplatin were determined using CCK-8. IGF1 secretion and expression were assayed via ELISA and western blot, respectively. A xenograft model was established, and pathological changes were detected by H&E staining. Proliferation and apoptosis-associated protein expression was assessed via IHC.
Results: Adipocytes promoted the viability and repressed cell apoptosis in OvCa, as well as enhancing platinum resistance, while the addition of IGF-1 R inhibitor reversed the effects of adipocytes on proliferation, apoptosis, and drug resistance of OvCa cells. Treatment with different concentrations of Ojeok-san (OJS) inhibited the adipocyte-induced platinum resistance in OvCa cells by suppressing IGF1. The combined treatment of OJS and cisplatin significantly inhibited tumour growth in vivo with good mouse tolerance.
Conclusion: In summary, OJS inhibited OvCa proliferation and platinum resistance by suppressing adipocyte paracrine IGF1 secretion.
期刊介绍:
Adipocyte recognizes that the adipose tissue is the largest endocrine organ in the body, and explores the link between dysfunctional adipose tissue and the growing number of chronic diseases including diabetes, hypertension, cardiovascular disease and cancer. Historically, the primary function of the adipose tissue was limited to energy storage and thermoregulation. However, a plethora of research over the past 3 decades has recognized the dynamic role of the adipose tissue and its contribution to a variety of physiological processes including reproduction, angiogenesis, apoptosis, inflammation, blood pressure, coagulation, fibrinolysis, immunity and general metabolic homeostasis. The field of Adipose Tissue research has grown tremendously, and Adipocyte is the first international peer-reviewed journal of its kind providing a multi-disciplinary forum for research focusing exclusively on all aspects of adipose tissue physiology and pathophysiology. Adipocyte accepts high-profile submissions in basic, translational and clinical research.