Transient receptor potential channel TRPC5 is essential for P-glycoprotein induction in drug-resistant cancer cells.
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 109 (2012-10-02), Heft 40, S. 16282-16287
academicJournal
Zugriff:
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. [ABSTRACT FROM AUTHOR]
Titel: |
Transient receptor potential channel TRPC5 is essential for P-glycoprotein induction in drug-resistant cancer cells.
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Autor/in / Beteiligte Person: | Ma, Xin ; Ca, Yanfei ; He, Dongxu ; Zou, Chang ; Zhang, Peng ; Lo, Chun Yin ; Xu, Zhenyu ; Chan, Franky L. ; Yu, Shan ; Chen, Yun ; Zhu, Ruiyu ; Lei, Jianyong ; Jin, Jian ; Yao, Xiaoqiang |
Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 109 (2012-10-02), Heft 40, S. 16282-16287 |
Veröffentlichung: | 2012 |
Medientyp: | academicJournal |
ISSN: | 0027-8424 (print) |
DOI: | 10.1073/pnas.1202989109 |
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