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FTY720 enhances chemosensitivity of colon cancer cells to doxorubicin and etoposide via the modulation of P ‐glycoprotein and multidrug resistance protein 1
Author(s) -
Xing Ying,
Wang Zhi Hong,
Ma Dong Hong,
Han Ying
Publication year - 2014
Publication title -
journal of digestive diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 51
eISSN - 1751-2980
pISSN - 1751-2972
DOI - 10.1111/1751-2980.12131
Subject(s) - etoposide , doxorubicin , p glycoprotein , multiple drug resistance , medicine , glycoprotein , colorectal cancer , pharmacology , cancer research , chemotherapy , cancer , drug resistance , biology , microbiology and biotechnology
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.