FTY720 enhances chemosensitivity of colon cancer cells to doxorubicin and etoposide via the modulation of P-glycoprotein and multidrug resistance protein 1.

Article Details

Citation

Copy to clipboard

Xing Y, Wang ZH, Ma DH, Han Y

FTY720 enhances chemosensitivity of colon cancer cells to doxorubicin and etoposide via the modulation of P-glycoprotein and multidrug resistance protein 1.

J Dig Dis. 2014 May;15(5):246-59. doi: 10.1111/1751-2980.12131.

PubMed ID

24868599 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Fingolimod	Multidrug resistance-associated protein 1	Protein	Humans	Unknown	Inhibitor Inducer	Details
Fingolimod	P-glycoprotein 1	Protein	Humans	No	Inhibitor	Details