Affiliation:
1. Department of Pharmacology SRMC, SRIHER, Porur, Chennai, Tamil Nadu 600116, India.
Abstract
In this study we evaluated the possible beneficial drug- interaction between Roflumilast (BCRP inhibitor) and Methotrexate (BCRP substrate) on viability of primary squamous cell carcinoma cell line using an in vitro technique. The KB cell line was treated with Roflumilast and Methotrexate to evaluate its anticancer activity using MTT assay. Image analysis under phase contrast microscopy was performed and flow-cytometry was done to see for cell cycle arrest as a result of drug treatment. Cell viability gradually decreased with the increasing concentrations of roflumilast, methotrexate and the cytotoxic effect with the combination of roflumilast and methotrexate also increased proportionally. Phase contrast microscopy indicated characteristic features of apoptosis which was confirmed in flow cytomtery and indicated cell cycle arrest in M phase. Efflux pump mediated multidrug resistance being a common feature among all cancers, the results of our study evidence the use of combined methotrexate and roflumilast to overcome drug resistance by exploiting the fact that the former is a BCRP substrate and latter a BCRP inhibitor. By combining the two drugs, it allows optimization of therapy by dose reduction of methotrexate and roflumilast and thereby resulting in better efficacy.
Publisher
Oriental Scientific Publishing Company
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