Loss of ABCB4 attenuates the caspase-dependent apoptosis regulating resistance to 5-Fu in colorectal cancer
Loss of ABCB4 attenuates the caspase-dependent apoptosis regulating resistance to 5-Fu in colorectal cancer
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DOI：
10.1042/bsr201714
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Xishan Wang
中科院分区：
文献类型：
--
作者：
Hanqing Hu;Meng Wang;Xu Guan;Ziming Yuan;Zheng Liu;Chaoxia Zou;Guiyu Wang;Xu Gao;Xishan Wang
The adenosine triphosphate-binding cassette (ABC) is a large group of proteins involved.in material transportation, cellular homeostasis, and closely associated with chemoresistance..ATP-binding cassette protein B4 (ABCB4) is a member of ABCs which has a similar.structure to ABCB1, but fewer researches were performed. The present study is aimed to.investigate the putative mechanism of ABCB4 in 5-fluorouracil (5-Fu) resistance. Then, we.found that ABCB4 was significantly down-regulated in the 5-Fu resistant HCT8 cell lines.by polymerase chain reaction (PCR) and Western blot. The knockdown of ABCB4 by small.interfering RNA decreased the apoptosis by 5-Fu in resistant HCT8R cell lines without influencing.the proliferation. Also, we found a lower expression of cleaved caspase and PARP.by Western blot after the knockdown of ABCB4. However, the knockdown of ABCB4 did not.influence the proliferation and apoptosis. Furthermore, the histological detection of ABCB4.mRNA level in human colorectal cancer tissues and even in the recurrent tissues after 5-Fu.single-agent chemotherapy was employed to provide more concrete evidence that ABCB4.may be a tumor suppressor gene to regulate chemoresistance in colorectal cancer. Moreover,.a 109-patient cohort revealed that ABCB4 predicted a poor recurrence-free survival.and overall survival. In summary, ABCB4 was down-regulated in the 5-Fu resistant cells and.knockdown of ABCB4 alleviated the cell apoptosis and predicts a shorter recurrence-free.survival and overall survival.
