ABT737 enhances cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics

	ABT737 enhances cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics
	Fan, Z. Q.; H. M. Yu; N. Cui; X. G. Kong; X. M. Liu; Y. L. Chang; Y. Wu; L. K. Sun and G. Y. Wang
	2015
发表期刊	Experimental Cell Research
卷号	335 期号:1 页码:68-81
摘要	Cholangiocarcinoma responses weakly to cisplatin. Mitochondrial dynamics participate in the response to various stresses, and mainly involve mitophagy and mitochondrial fusion and fission. Bcl-2 family proteins play critical roles in orchestrating mitochondrial dynamics, and are involved in the resistance to cisplatin. Here we reported that ABT737, combined with cisplatin, can promote cholangiocarcinoma cells to undergo apoptosis. We found that the combined treatment decreased the Mcl-1 pro-survival form and increased Bak. Cells undergoing cisplatin treatment showed hyperfused mitochondria, whereas fragmentation was dominant in the mitochondria of cells exposed to the combined treatment, with higher Fis1 levels, decreased Mfn2 and OPA1 levels, increased ratio of Drp1 60 kD to 80 kD form, and more Drp1 located on mitochondria. More p62 aggregates were observed in cells with fragmented mitochondria, and they gradually translocated to mitochondria. Mitophagy was induced by the combined treatment. Knockdown p62 decreased the Drp1 ratio, increased Tom20, and increased cell viability. Our data indicated that mitochondrial dynamics play an important role in the response of cholangiocarcinoma to cisplatin. ABT737 might enhance cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics and the balance within Bcl-2 family proteins. Furthermore, p62 seems to be critical in the regulation of mitochondrial dynamics. 2015 Elsevier Inc. All rights reserved.
收录类别	SCI
文献类型	期刊论文
条目标识符	http://ir.ciomp.ac.cn/handle/181722/55231
专题	中科院长春光机所知识产出
推荐引用方式 GB/T 7714	Fan, Z. Q.,H. M. Yu,N. Cui,et al. ABT737 enhances cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics[J]. Experimental Cell Research,2015,335(1):68-81.
APA	Fan, Z. Q..,H. M. Yu.,N. Cui.,X. G. Kong.,X. M. Liu.,...&L. K. Sun and G. Y. Wang.(2015).ABT737 enhances cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics.Experimental Cell Research,335(1),68-81.
MLA	Fan, Z. Q.,et al."ABT737 enhances cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics".Experimental Cell Research 335.1(2015):68-81.

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