SREBP1 promotes 5-FU resistance in colorectal cancer cells by inhibiting the expression of caspase7

SREBP1通过抑制caspase7的表达促进结直肠癌细胞产生5-FU耐药性

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作者:Yuyan Gao, Qi Zhao, Xiaoqin Mu, Huifen Zhu, Binbin Liu, Bingqing Yao, Xinyi Liu, Wenhan Xue, Bo Wang, Shulin Liu

Background

The role of lipid metabolism played in cancer cell growth attracts more attention. SREBP1 is a common lipid regulatory factor. It has been reported that SREBP1 can promote tumor cell resistance. The

Conclusion

Our results suggest that SREBP1 protect the 5-FU treated CRC cells through caspase7 dependent PARP1 cleavage in apoptosis pathway and potentially provide a new target in the treatment of CRC.

Methods

The expression of SREBP1 in CRC tissues was analyzed by immunohistochemistry. Using a viability assay, the sensitivity to 5-fluorouracil in two colon cancer cell lines (HT-29 and SW620) was measured and its correlation with different expression levels of SREBP1 protein by western blot was investigated.

Results

The protein expression of SREBP1 in CRC tissues was higher than that in normal colon tissues. We found that over-expression of SREBP1 through SREBP1 gene transfection enhances the resistant of CRC cell lines to 5-FU, and SREBP1 silencing through SREBP1 shRNA transfection can promote apoptosis in 5-FU treated SW620 cells. Further study indicated that SREBP1 could inhibit the expression of caspase7 and reduce PARP1 cleavage fragments.

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