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广泛分析与卵巢癌进展和化疗耐药相关的 G 蛋白信号转导调节因子 10 调节在临床和体外模型中的作用。

A broad analysis in clinical and in vitro models on regulator of G-protein signalling 10 regulation that is associated with ovarian cancer progression and chemoresistance.

机构信息

Department of Molecular Biology and Genetics, Tokat Gaziosmanpasa University, Tokat, Turkey.

出版信息

Cell Biochem Funct. 2021 Apr;39(3):413-422. doi: 10.1002/cbf.3607. Epub 2020 Dec 22.

Abstract

Ovarian cancer is one of the deadliest types of gynaecological cancers and more than half of the patients die within 5 years after diagnosis. Recurrence in advanced staged patients after chemotherapy is associated with increased chemoresistance, which results in poor prognosis. Regulator of G-protein signalling 10 (RGS10) negatively regulates cell proliferation, migration and survival by attenuating G-protein coupled-receptors mediated signalling pathways. Recent studies have shown that loss of RGS10 expression is significantly associated with proliferation and cisplatin resistance in ovarian cancer cells. SIGNIFICANCE OF THE STUDY: In this study, we analysed differential RGS10 expression levels using public microarray datasets from clinical and in vitro ovarian cancer samples. We validated that cancer progression and chemotherapy exposure change RGS10 expression. We enriched our study to evaluate the relationship between chemoresistance and differential RGS10 expression against ovarian cancer potential chemotherapeutic agent, palbociclib. Results showed that palbociclib treatment reduced cell viability, despite significantly decreased RGS10 expression in chemoresistant cells. Overall, the results confirmed that cancer progression and chemoresistance are significantly associated with the down-regulation of RGS10 while some chemotherapeutics seem to be beneficial in decreasing chemoresistance in ovarian cancer.

摘要

卵巢癌是妇科癌症中最致命的类型之一,超过一半的患者在诊断后 5 年内死亡。化疗后晚期患者的复发与化疗耐药性增加有关,这导致预后不良。G 蛋白信号转导调节因子 10(RGS10)通过减弱 G 蛋白偶联受体介导的信号通路,负调控细胞增殖、迁移和存活。最近的研究表明,RGS10 表达缺失与卵巢癌细胞的增殖和顺铂耐药性显著相关。研究意义:在这项研究中,我们使用来自临床和体外卵巢癌样本的公共微阵列数据集分析了差异的 RGS10 表达水平。我们验证了癌症进展和化疗暴露改变了 RGS10 的表达。我们进一步研究评估了 RGS10 表达的差异与卵巢癌潜在化疗药物帕博西利的耐药性之间的关系。结果表明,尽管耐药细胞中 RGS10 的表达显著降低,但帕博西利治疗仍降低了细胞活力。总的来说,这些结果证实了癌症进展和化疗耐药性与 RGS10 的下调显著相关,而一些化疗药物似乎有利于降低卵巢癌的化疗耐药性。

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