Combination of oncolytic adenovirus and dacarbazine enhances antitumor ability against uveal melanoma cells via cell cycle block

Abstract

Uveal melanoma is the most common primary intraocular malignancy in adults; however, current therapeutic modalities, including chemotherapy, have not been successful. Oncolytic viruses serve as an emerging gene therapy tool for cancer treatment because they specifically kill tumor cells while sparing normal cells. The oncolytic virus H101 has been approved by the Chinese State Food and Drug Administration for the treatment of certain malignancies. Unfortunately, the monotherapy of adenovirus has demonstrated limited efficacy in a clinical setting. Thus, novel treatment strategies in which an oncolytic virus is combined with existing chemicals are advancing toward potential clinical use. In this study, we chose the combination of oncolytic virus H101 and the alkylating agent dacarbazine (DTIC) to treat uveal melanoma cells in vitro. Our results demonstrated that the combination exerted a synergistic antitumor effect without enhanced toxicity to normal cells via a type of cell cycle block other than the induction of apoptosis. Further investigation is warranted to elucidate the specific underlying mechanisms of this co-treatment therapy. Our study suggests the viro-chemo combination therapy is feasible and is a potentially promising approach for the treatment of uveal melanoma.

Keywords: :

• cell cycle
• combination therapy
• dacarbazine
• oncolytic adenovirus
• uveal melanoma

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

This work was supported by the National Key Program for Basic Research of China grant (2010CB529902), The National Natural Science Foundation of China grant (10979034, 81001008), The Science and Technology Commission of Shanghai (10JC1409100), the Shanghai Rising-Star Program(11QA1404000), and the Shanghai Leading Academic Discipline Project grant (S30205).