Transient receptor potential channel TRPC5 is essential for P-glycoprotein induction in drug-resistant cancer cells
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AbstractAn attractive strategy to overcome multidrug resistance in cancer chemotherapy is to suppress P-glycoprotein (P-gp), which is a pump overproduced in cancer cells to remove cytotoxic drugs from cells. In the present study, a Ca2+-permeable channel TRPC5 was found to be overproduced together with P-gp in adriamycin-resistant breast cancer cell line MCF-7/ADM. Suppressing TRPC5 activity/expression reduced the P-gp induction and caused a remarkable reversal of adriamycin resistance in MCF-7/ADM. In an athymic nude mouse model of adriamycin-resistant human breast tumor, suppressing TRPC5 decreased the growth of tumor xenografts. Nuclear factor of activated T cells isoform c3 (NFATc3) was the transcriptional factor that links the TRPC5 activity to P-gp production. Together, we demonstrated an essential role of TRPC5-NFATc3-P-gp signaling cascade in P-gp induction in drug-resistant cancer cells.
All Author(s) ListMa X, Cai YF, He DX, Zou C, Zhang P, Lo CY, Xu ZY, Chan FL, Yu S, Chen Y, Zhu RY, Lei JY, Jin J, Yao XQ
Journal nameProceedings of the National Academy of Sciences
Volume Number109
Issue Number40
Pages16282 - 16287
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesMultidisciplinary Sciences; MULTIDISCIPLINARY SCIENCES; Science & Technology - Other Topics

Last updated on 2021-16-09 at 01:00