期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 138, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2021.111407
关键词
Paclitaxel; Ovarian cancer; ClC-3 chloride channel; Tubulin
资金
- National Natural Science Foundation of China [81372382, 81872133]
- Students Research Training Program Fund of Guangdong Province [201910559049]
- Project of Traditional Chinese Medicine [20182025]
Over-expression of ClC-3 protein in PTX-resistant ovarian cancer cells promotes the combination of ClC-3 and beta-tubulin, reducing sensitivity to PTX.
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 beta-tubulin, whereas the beta-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 beta-tubulin, and the possibility of proteins interaction between ClC-3 and beta-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 beta-tubulin, which in turn increase the ration of free form and decrease the quota of the polymeric form of beta-tubulin, and finally reduce the sensitivity to PTX. Our findings elucidated a novel function of ClC-3 in regu-lating PTX resistance and ClC-3 could serve as a potential target to overcome the PTX resistance ovarian cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据