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二甲双胍可增强奥拉帕利在膀胱癌细胞中的抑制作用。

Metformin Can Enhance the Inhibitory Effect of Olaparib in Bladder Cancer Cells.

机构信息

Department of Urology, The First Affiliated Hospital of Jiamusi University, China.

Department of Vascular Surgery, The First Affiliated Hospital of Jiamusi University, China.

出版信息

Dis Markers. 2022 Jun 24;2022:5709259. doi: 10.1155/2022/5709259. eCollection 2022.

Abstract

BACKGROUND

Bladder cancer is a common urinary system tumor. In the treatment of clinical patients, it is particularly important to find an effective treatment method to inhibit tumor growth. The world's first PARP inhibitor olaparib is mainly used for the treatment of BRCA1/BRCA2 mutated tumors. Metformin, an antidiabetic drug, has been reported to reduce cancer incidence in humans and improve survival in cancer patients.

METHODS

Cell viability and proliferation were detected by CCK-8 assay and colony formation assay; cell apoptosis was detected by flow cytometry; cell migration and invasion abilities were detected by scratch assay and Transwell assay; STAT3/C-MYC signaling pathway protein were detected by western blotting.

RESULTS

Olaparib combined with metformin has better effects on the proliferation, clone formation, migration, invasion, and apoptosis of bladder cancer cells than single drug, indicating that metformin can enhance the inhibitory effect of olaparib on tumor growth and regulate the expression of STAT3/C-MYC signaling pathway proteins.

CONCLUSION

The results of this study showed that metformin could significantly enhance the antitumor effect of olaparib on bladder cancer cells, and these effects were mediated by downregulating STAT3/C-MYC signaling pathway proteins. This finding may have potential clinical application in the treatment of bladder cancer.

摘要

背景

膀胱癌是一种常见的泌尿系统肿瘤。在临床患者的治疗中,找到一种有效的治疗方法来抑制肿瘤生长尤为重要。世界上第一种 PARP 抑制剂奥拉帕利主要用于治疗 BRCA1/BRCA2 突变型肿瘤。降糖药物二甲双胍已被报道可降低人类癌症发病率并改善癌症患者的生存。

方法

通过 CCK-8 检测和集落形成实验检测细胞活力和增殖;通过流式细胞术检测细胞凋亡;通过划痕实验和 Transwell 实验检测细胞迁移和侵袭能力;通过 Western blot 检测 STAT3/C-MYC 信号通路蛋白。

结果

奥拉帕利联合二甲双胍对膀胱癌细胞的增殖、克隆形成、迁移、侵袭和凋亡的作用优于单药,表明二甲双胍可增强奥拉帕利对肿瘤生长的抑制作用,并调节 STAT3/C-MYC 信号通路蛋白的表达。

结论

本研究结果表明,二甲双胍可显著增强奥拉帕利对膀胱癌细胞的抗肿瘤作用,这些作用是通过下调 STAT3/C-MYC 信号通路蛋白介导的。这一发现可能在膀胱癌的治疗中有潜在的临床应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8b7/9249502/72b550e37f36/DM2022-5709259.001.jpg

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