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- Title
FTY720 enhances chemosensitivity of colon cancer cells to doxorubicin and etoposide via the modulation of P-glycoprotein and multidrug resistance protein 1.
- Authors
Xing, Ying; Wang, Zhi Hong; Ma, Dong Hong; Han, Ying
- Abstract
Objective This study aimed to investigate the effects of FTY720 on inducing cell growth inhibition and enhancing the cytotoxicity of anti-cancer drugs in the human colon cancer cell line HCT-8 and its multidrug-resistant cell line HCT-8/5-fluorouracil ( HCT-8/5- Fu). Methods Cell viability and apoptosis after being treated with FTY720 alone or in combination with doxorubicin ( DOX) and etoposide ( VP16) were tested in HCT-8 and HCT-8/5- Fu cells. The changes in P-glycoprotein ( P-gp) and multidrug resistance protein 1 ( MRP1) were determined at the mRNA and functional levels. Results FTY720 showed anti-proliferative activity against cancer cells in a dose-dependent and time-dependent manner and could enhance the cytotoxicity of DOX and VP16 in both HCT-8 and HCT-8/5- Fu cell lines. In addition, treatment with FTY720 resulted in the promotion of VP16-induced cell apoptosis and an increased accumulation of intracellular DOX and two specific fluorescent substrates of P-gp and MRP1 through the inhibition of efflux and the suppression of gene expression. Conclusion FTY720 exerts its chemosensitization effect in HCT-8 and HCT-8/5- Fu cell lines by promoting cell apoptosis and inhibiting P-gp and MRP1, which could be applied as a potential co-adjuvant therapeutic modality.
- Subjects
GROWTH factors; DOXORUBICIN; ETOPOSIDE; MESSENGER RNA; APOPTOSIS; THERAPEUTICS
- Publication
Journal of Digestive Diseases, 2014, Vol 15, Issue 5, p246
- ISSN
1751-2972
- Publication type
Article
- DOI
10.1111/1751-2980.12131