ClC-3 promotes paclitaxel resistance via modulating tubulins polymerization in ovarian cancer cells.

Jiezhu Feng, Zihan Peng, Lvfen Gao, Xiurou Yang, Zele Sun, Xiuying Hou, Enze Li, Linyan Zhu, Haifeng Yang

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2021 Jun

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Epithelial ovarian cancers (EOC) present as malignant tumors with high mortality in the female reproductive system diseases. Acquired resistance to paclitaxel (PTX), one of the first-line treatment of EOC, remains a therapeutic challenge. ClC-3, a member of the voltage-gated Cl- channels, plays an essential role in a variety of cellular activities, including chemotherapeutic resistance. Here, we demonstrated that the protein expression and channel function of ClC-3 was upregulated in PTX resistance A2780/PTX cells compared with its parental A2780 cells. The silence of ClC-3 expression by siRNA in A2780/PTX cells partly recovered the PTX sensitivity through restored the G2/M arrest and resumed the chloride channel blocked. ClC-3 siRNA both inhibited the expression of ClC-3 and β-tubulin, whereas the β-tubulin siRNA reduced the expression of itself only, without affecting the expression of ClC-3. Moreover, treatment of ClC-3 siRNA in A2780/PTX cells increased the polymerization ratio of β-tubulin, and the possibility of proteins interaction between ClC-3 and β-tubulin was existing. Take together, the over-expression of ClC-3 protein in PTX-resistance ovarian cancer cells promotes the combination of ClC-3 and β-tubulin, which in turn increase the ration of free form and decrease the quota of the polymeric form of β-tubulin, and finally reduce the sensitivity to PTX. Our findings elucidated a novel function of ClC-3 in regulating PTX resistance and ClC-3 could serve as a potential target to overcome the PTX resistance ovarian cancer. Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Citation

Jiezhu Feng, Zihan Peng, Lvfen Gao, Xiurou Yang, Zele Sun, Xiuying Hou, Enze Li, Linyan Zhu, Haifeng Yang. ClC-3 promotes paclitaxel resistance via modulating tubulins polymerization in ovarian cancer cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2021 Jun;138:111407