Targeting Mcl-1 inhibits survival and self-renewal of hepatocellular cancer stem-like cells

靶向 Mcl-1 可抑制肝细胞癌干细胞样细胞的存活和自我更新

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作者:Huapeng Zhang, Gongquan Li, Guanghui Chen, Yi Zhang, Jie Pan, Hongwei Tang, Jie Li, Wenzhi Guo, Shuijun Zhang

Abstract

Myeloid cell leukemia-1 (Mcl-1) is highly expressed in tumor tissues and cells of hepatocellular carcinoma (HCC), yet the role of Mcl-1 in cancer stem-like cells (CSLCs) remains largely unclear. Herein, we showed that knockdown of Mcl-1 significantly inhibited HCC cells to form spheres under ultra-low attachment condition in serum-free medium, and also attenuated clone formation. Inhibition of Mcl-1 by specific inhibitors S63845 or A-1210477 hindered secondary sphere formation, triggered apoptosis signaling and reduced the level of stem cell transcription factor Nanog, Sox2 and KLF4 in HCC spheroids cells. This study suggests that Mcl-1 is an essential factor for the survival and self-renewal of HCC CSLCs.

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