Chloride channel-3 mediates multidrug resistance of cancer by upregulating P-glycoprotein expression.

Author(s) Chen, Q.; Liu, X.; Luo, Z.; Wang, S.; Lin, J.; Xie, Z.; Li, M.; Li, C.; Cao, H.; Huang, Q.; Mao, J.; Xu, B.
Journal J Cell Physiol
Date Published 2019 May
Abstract

Chloride channel-3 (ClC-3), a member of the ClC family of voltage-gated Cl channels, is involved in the resistance of tumor cells to chemotherapeutic drugs. Here, we report a new mechanism for ClC-3 in mediating multidrug resistance (MDR). ClC-3 was highly expressed in the P-glycoprotein (P-gp)-dependent human lung adenocarcinoma cell line (A549)/paclitaxel (PTX) and the human breast carcinoma cell line (MCF-7)/doxorubicin (DOX) resistant cells. Changes in the ClC-3 expression resulted in the development of drug resistance in formerly drug-sensitive A549 or MCF-7 cells, and drug sensitivity in formerly drug-resistant A549/Taxol and MCF-7/DOX cells. Double transgenic MMTV-PyMT/CLCN3 mice with spontaneous mammary cancer and ClC-3 overexpression demonstrated drug resistance to PTX and DOX. ClC-3 expression upregulated the expression of MDR1 messenger RNA and P-gp by activating the nuclear factor-κB (NF-κB)-signaling pathway. These data suggest that ClC-3 expression in cancer cells induces MDR by upregulating NF-κB-signaling-dependent P-gp expression involving another new mechanism for ClC-3 in the development of drug resistance of cancers.

DOI 10.1002/jcp.27402
ISSN 1097-4652
Citation Chen Q, Liu X, Luo Z, Wang S, Lin J, Xie Z, et al. Chloride channel-3 mediates multidrug resistance of cancer by upregulating P-glycoprotein expression. J Cell Physiol. 2019;234(5):6611-6623.

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