Evaluation of PDE4 Inhibitor Roflumilast For The Treatment of Colon Cancer

Abstract

Background Colon cancer remains the fourth most cause of cancer worldwide. Despite novel technologies, colon cancer remains undiagnosed and 25% of patients are diagnosed with metastatic colon cancer. Phosphodiesterase is a group of isoenzyme, which, hydrolyze cyclic nucleotides and thereby lowers intracellular levels of cAMP and cGMP leading to tumorigenic effects. Many in vitro and in vivo studies have confirmed increased PDE expression in different types of cancers including colon cancer which can be used as a target for colon cancer treatment. In public dataset analysis of 16 patients in which patients (n=6) with relapsed CRC have acquired higher expression of PDE4B mRNA than that of the non-relapsed CRC patients (n=10), suggesting poor prognosis and metastasis of CRC is associated with higher PDE4B expression. Hence, we have evaluated the effect of roflumilast, PDE4B inhibitor, for the treatment of colon cancer and tried to evaluate the possible mechanism behind its anti-cancer efficacy. Materials and methods: In vitro evaluation In vitro studies were carried out using HCT-116 cell lines. In vitro cell viability assay (MTT assay) was performed for evaluating IC50 of the drug.