4.5 Article

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

Journal

CANCER BIOLOGY & THERAPY
Volume 13, Issue 2, Pages 77-84

Publisher

LANDES BIOSCIENCE
DOI: 10.4161/cbt.13.2.18436

Keywords

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

Categories

Funding

  1. National Key Program for Basic Research of China [2010CB529902]
  2. National Natural Science Foundation of China [10979034, 81001008]
  3. Science and Technology Commission of Shanghai [10JC1409100]
  4. Shanghai Rising-Star Program [11QA1404000]
  5. Shanghai Leading Academic Discipline Project [S30205]

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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.

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