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A comparison analysis of anti-tumor efficacy of adenoviral gene replacement therapy (p14ARF and p16INK4A) in human mesothelioma cells.

BACKGROUND
Tumor suppressor genes encode critical cell cycle regulatory proteins that are frequently mutated or deleted in cancer and, therefore, are important candidates for cancer treatment based on gene replacement strategies.


MATERIALS AND METHODS
We evaluated and compared the relative potential therapeutic efficacy of p14ARF and p16INK4A expressed in adenoviral vectors (Adp14ARF and Adp16INK4A, respectively) in three human mesothelioma cell lines.


RESULTS
The cytotoxic effects of expressed p16INK4A were significantly greater than that of p14ARF in both H28 and H2052 cells. Cell cycle G1 arrest occurred earlier with Adp16INK4A treatment than Adp14ARF (24 hours vs. 48 hours, respectively). Although both Adp14ARF and Adp16INK4A inhibited cell proliferation significantly and were potentiated by chemotherapy, Adp16INK4A appeared more potent.


CONCLUSION
Our results suggest that adenoviral gene-based therapy, especially using Adp16INK4A-based strategy, may be effective in the treatment of human mesothelioma.