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Journal of Zhejiang University SCIENCE B

ISSN 1673-1581(Print), 1862-1783(Online), Monthly

Potential effect of EGCG on the anti-tumor efficacy of metformin in melanoma cells

Abstract: Metformin, a first-line drug for type 2 diabetes mellitus, has been recognized as a potential anti-tumor agent in recent years. Epigallocatechin-3-gallate (EGCG), as the dominant catechin in green tea, is another promising adjuvant agent for tumor prevention. In the present work, the potential effect of EGCG on the anti-tumor efficacy of metformin in a mouse melanoma cell line (B16F10) was investigated. Results indicated that EGCG and metformin exhibited a synergistic effect on cell viability, migration, and proliferation, as well as signal transducer and activator of transcription 3/nuclear factor-κB (STAT3/NF-κB) pathway signaling and the production of inflammation cytokines. Meanwhile, the combination showed an antagonistic effect on cell apoptosis and oxidative stress levels. The combination of EGCG and metformin also differentially affected the nucleus (synergism) and cytoplasm (antagonism) of B16F10 cells. Our findings provide new insight into the potential effects of EGCG on the anti-tumor efficacy of metformin in melanoma cells.

Key words: Epigallocatechin-3-gallate (EGCG); Metformin; Melanoma; Anti-tumor efficacy

Chinese Summary  <32> 表没食子儿茶素-3-没食子酸酯(EGCG)对二甲双胍抗黑素瘤细胞的潜在影响

目的:探明表没食子儿茶素-3-没食子酸酯(EGCG)联合二甲双胍对高转移性小鼠黑素瘤细胞系B16F10活力、迁移和增殖等生长状态以及信号传导与转录活化因子3/核因子κB(STAT3/NF-κB)信号通路的作用,并利用拉曼光谱等分析EGCG和二甲双胍联合作用的潜在机制。
创新点:(1)EGCG联合二甲双胍对B16F10细胞活力、增殖以及STAT3/NF-κB信号通路等具有协同抑制作用;(2)EGCG联合二甲双胍在B16F10细胞凋亡和氧化应激方面具有拮抗作用;(3)利用拉曼光谱分析技术发现EGCG与二甲双胍联用对B16F10细胞的细胞核和细胞质存在差异化影响。
方法:利用CCK8测定细胞增殖,用细胞划痕实验测定细胞运动特性,利用流式细胞仪分析凋亡和细胞周期,利用免疫组织化学染色法观察细胞切片,用酶联免疫吸附试验(ELISA)测定炎症细胞因子和抗氧化酶的蛋白水平含量,用定量逆转录聚合酶链反应(qRT-PCR)检测其基因水平含量,用蛋白质印迹(western blot)探究其可能影响的细胞通路,用拉曼光谱技术从亚细胞水平探究作用机制。
结论:本研究表明EGCG与二甲双胍联合作用在抑制B16F10细胞生长、炎症水平和STAT3/NF-κB通路方面发挥部分协同效应。然而,这两种化合物对B16F10细胞凋亡和氧化应激具有拮抗作用。为了进一步证实EGCG和二甲双胍对黑色素瘤潜在的联合作用,还需要进一步研究EGCG和二甲双胍的药效学相互作用。

关键词组:表没食子儿茶素-3-没食子酸酯(EGCG);二甲双胍;黑色素瘤;抗肿瘤功效


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DOI:

10.1631/jzus.B2000455

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On-line Access:

2024-08-27

Received:

2023-10-17

Revision Accepted:

2024-05-08

Crosschecked:

2022-04-22

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