期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 40, 页码 16282-16287出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1202989109
关键词
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资金
- Hong Kong Research Grants Council [CUHK479109, CUHK478710, CUHK478011]
- Chinese University of Hong Kong
- Chinese Academy of Sciences [XDA01040000]
- Ministry of Science and Technology of China [2011CB966200]
- China National Natural Science Foundation [81100185, 81130057, 81101667]
- Jiangsu Province Natural Science Foundation [BK2009071]
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.
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