Low-dose paclitaxel downregulates MYC proto-oncogene bHLH transcription factor expression in colorectal carcinoma cells

低剂量紫杉醇下调结直肠癌细胞MYC原癌基因bHLH转录因子的表达

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作者:Wenjing Li, Wanyun Zhu, Chaoxiang Lv, Hao Qu, Kaixiang Xu, Honghui Li, Haifeng Li, Yiming Du, Guangming Liu, Yunyue Wang, Hong-Jiang Wei, Hong-Ye Zhao

Abstract

Paclitaxel (PTX) has been commonly used to treat multiple types of tumor. Its anticancer mechanism differs based on different PTX concentrations and types of tumor cell. In the present study, MTT assays of HCT116 and LOVO cells treated with PTX revealed the chemosensitivity of the cell lines for different PTX concentrations. The half-maximal inhibitory concentration values of PTX for these cells were 2.46 and 2.24 nM, respectively. Cell morphology observation revealed that both cell lines exhibited rounded, wrinkled and damaged morphologies with increasing concentrations of PTX. Fluorescence-activated cell sorting analysis indicated that 1 nM PTX increased the proportion of cells in sub-G1 phases and decreased the proportion of cells in G0/G1 phases, whereas the proportions of cells in S and G2/M phases only slightly changed for both cell lines. Western blot analysis indicated that the total/nuclear protein expression of MYC proto-oncogene bHLH transcription factor (c-Myc) and phosphorylated (P)-c-Myc decreased in HCT116 cells in a dose-dependent manner, whereas the nuclear protein expression of P-c-Myc increased in LOVO cells in a dose-dependent manner. These results suggest that low-dose PTX downregulates c-Myc and P-c-Myc expression, subsequently inhibiting the cell cycle at G0/G1 in colorectal carcinoma.

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