Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China.
Medical School, Guangxi University, Nanning 530004, China.
Biomolecules. 2023 Jun 6;13(6):950. doi: 10.3390/biom13060950.
Metformin is a traditional antidiabetic drug that also shows potential antitumor effects in cervical cancer. However, some of its apoptosis-related mechanisms are still unclear. In this study, flow cytometry, western blotting, and RNA sequencing (RNA-seq) were used to evaluate the molecular mechanisms of metformin in HeLa cells. The results showed that metformin inhibited cell viability and promoted apoptosis, the protein expression level of Caspase-3 (CASP3) was increased and that of BCL-2 was decreased in HeLa cells treated with metformin. The RNA-seq results indicated a total of 239 differentially expressed genes between the metformin and control check (CK) groups, with 136 genes upregulated and 103 genes downregulated, and 14 of them were found to be associated with apoptosis signaling pathways. The and genes were robustly upregulated in HeLa cells by the endoplasmic reticulum (ER) stress and the mitochondrial pathway of apoptosis. Metformin also affects the expression of , , and , which participate in biological processes such as PI3K-AKT, mTOR, and AMPK signaling pathways. Metformin mediates the expression of related genes to induce apoptosis.
二甲双胍是一种传统的抗糖尿病药物，在宫颈癌中也显示出潜在的抗肿瘤作用。然而，其一些与细胞凋亡相关的机制尚不清楚。本研究采用流式细胞术、Western blot 和 RNA 测序（RNA-seq）评估二甲双胍在 HeLa 细胞中的分子机制。结果表明，二甲双胍抑制细胞活力并促进细胞凋亡，用二甲双胍处理的 HeLa 细胞中 Caspase-3（CASP3）蛋白表达水平升高，BCL-2 蛋白表达水平降低。RNA-seq 结果表明，二甲双胍组和对照检查（CK）组之间共有 239 个差异表达基因，其中 136 个基因上调，103 个基因下调，其中 14 个基因与细胞凋亡信号通路有关。内质网（ER）应激和线粒体凋亡途径使 和 基因在 HeLa 细胞中显著上调。二甲双胍还影响参与 PI3K-AKT、mTOR 和 AMPK 信号通路等生物学过程的 、 和 的表达。二甲双胍通过调节相关基因的表达诱导细胞凋亡。
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