Ojeok-san enhances platinum sensitivity in ovarian cancer by regulating adipocyte paracrine IGF1 secretion.

IF 3.5 4区生物学 Q2 ENDOCRINOLOGY & METABOLISM Adipocyte Pub Date : 2024-12-01 Epub Date: 2023-11-22 DOI:10.1080/21623945.2023.2282566

Jiong Ma, Junyan Li, Xuejun Chen, Yanyan Ma

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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.

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Ojeok-san通过调节脂肪细胞旁分泌IGF1分泌增强卵巢癌的铂敏感性。

背景:铂是卵巢癌(OvCa)治疗的常用药物，但耐药限制了其临床应用。本研究旨在描述脂肪细胞对OvCa铂耐药的影响。方法:OvCa细胞保存在脂肪细胞条件培养基中。分别用CCK-8和流式细胞术检测细胞活力和凋亡。western blot检测细胞增殖和凋亡相关蛋白的表达。采用CCK-8测定顺铂和卡铂的IC50值。分别用ELISA和western blot检测IGF1的分泌和表达。建立异种移植物模型，H&E染色检测病理变化。通过免疫组化检测细胞增殖和凋亡相关蛋白的表达。结果:脂肪细胞促进OvCa细胞活力，抑制细胞凋亡，增强铂耐药，而添加IGF-1 R抑制剂逆转了脂肪细胞对OvCa细胞增殖、凋亡和耐药的影响。不同浓度的OJS通过抑制IGF1抑制脂肪细胞诱导的OvCa细胞铂耐药。OJS与顺铂联合治疗在体内显著抑制肿瘤生长，小鼠耐受性良好。结论:综上所述，OJS通过抑制脂肪细胞旁分泌IGF1的分泌来抑制OvCa增殖和铂耐药。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Adipocyte Medicine-Histology

CiteScore

6.50

自引率

3.00%

发文量

审稿时长

32 weeks

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.