Transient receptor potential channel TRPC5 is essential for P-glycoprotein induction in drug-resistant cancer cells
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摘要An 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.
著者Ma 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
期刊名稱Proceedings of the National Academy of Sciences
出版年份2012
月份10
日期2
卷號109
期次40
出版社NATL ACAD SCIENCES
頁次16282 - 16287
國際標準期刊號0027-8424
語言英式英語
Web of Science 學科類別Multidisciplinary Sciences; MULTIDISCIPLINARY SCIENCES; Science & Technology - Other Topics

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