Forskolin enhances the antitumor effect of oncolytic measles virus by promoting Rab27a dependent vesicular transport system in the lung cancer A549 cells in vitro
Abstract Background: Measles vaccine strain viruses (MV-Edm) are an ideal platform for developing safe and effective oncolytic vectors. However, despite the promising pre-clinical data, understanding of determinants of efficacy and, thus, the interplay of the oncolytic virus with particular agents remains limited.Methods: We investigated the potency of forskolin enhancing the antitumor effect of oncolytic measles virus by promoting Rab27a dependent vesicular transport system. Cells were infected with MV-Edm and the vesicles were observed by TEM. The oncolytic effects of MV-Edm/Forskolin were investigated in vitro. Results: Here we demonstrate that the MV-Edm infection and spread in tumor, which are indispensable processes for the viral oncolysis, depend on the vesicular transport system of tumor cells. On the contrary, the tumor cells display a responsive mechanism to restrain the MV-Edm spread by down-regulating the expression of Rab27a, which is a key member of the vesicle transport system. Over-expression of Rab27a promotes the oncolytic efficacy of MV-Edm towards A549 tumor cells. Finally, we find a Rab27a agonist Forskolin, is capable of promoting the oncolytic effect of MV-Edm in vitro. Conclusions: Our study reveals the important role of vesicle transporter Rab27a in the whole program of MV-Edm mediated oncolysis. We also provide a combined strategy of Forskolin and MV-Edm, which may exert a synergistic anti-tumor effect, for clinical treatment for patients with tumor.