4.6 Article

Metformin sensitizes AML cells to venetoclax through endoplasmic reticulum stress-CHOP pathway

期刊

BRITISH JOURNAL OF HAEMATOLOGY
卷 -, 期 -, 页码 -

出版社

WILEY
DOI: 10.1111/bjh.18968

关键词

acute myeloid leukaemia; apoptosis; CHOP; endoplasmic reticulum stress; metformin

向作者/读者索取更多资源

The combination of metformin and venetoclax has been found to effectively inhibit the growth of AML cells both in vitro and in vivo. This combination treatment induces cell apoptosis and increases the expression levels of the endoplasmic reticulum stress-related marker CHOP, which plays a crucial role in the anti-leukemic activity.
Venetoclax inhibits acute myeloid leukaemia by inhibiting BCL-2 targeting, and a combination regimen with venetoclax has been explored. Although these regimens produce better clinical results, the vast majority of patients still suffer from disease recurrence or primary drug resistance. Metformin has been demonstrated to induce apoptosis in cancer cells. However, whether it can synergize with venetoclax and the underlying mechanisms of metformin-induced apoptosis are not fully understood. In this study, we investigated the effect of metformin and venetoclax on the growth of AML cells in vitro and in vivo. In both Molm13 and THP-1 cell lines, metformin and venetoclax synergistically inhibited the proliferation and induced apoptosis of leukaemia cells. Most importantly, the combination of metformin and venetoclax treatment significantly increased the expression levels of the endoplasmic reticulum (ER) stress-related marker CHOP, for example, in AML cell lines. Knockdown of CHOP markedly attenuated the metformin- and venetoclax-induced cell apoptosis. Moreover, the combination of metformin and venetoclax demonstrated prominent anti-leukaemia effects in xenograft models and bone marrow samples from AML patients. In summary, the combination of metformin and venetoclax showed enhanced anti-leukaemia activity with acceptable safety in AML patients, representing a new combinatorial strategy worth further clinical investigation to treat AML.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据