Exogenous PUMA Sensitizes HPV Positive Cervical Cancer Cells To Irradiation In Vitro

Objective:Cervical cancer is the second most common malignancy in women worldwide.Human papilloma virus(HPV) infection is the most important risk factor of cervical cancer.PUMA was recently identified as a mediator of DNA damage-induced and p53-dependent apoptosis.In this study,we investigated whether exogenous PUMA suppresses the growth of HPV positive cervical cancer and sensitizes HPV positive cervical cancer cells to irradiation.Methods:An adenovirus expressing PUMA(Ad-PUMA),alone or in combination with irradiation,was used to treat HPV positive cervical cancer cells HeLa and CaSki. The growth inhibitory and pro-apoptotic effects of PUMA in vitro were examined.The efficacy of PUMA and p53 in suppressing the growth of HeLa and CaSki were also compared.The expression of PUMA was examined in HeLa cell treated with irradiation.Results:RT-PCR and Western Blot revealed that the expression of exogenous PUMA was elevated 3 hours after infection.Ad-PUMA suppressed the growth of HPV positive cervical cancer cells,and was more efficient than Ad-p53.Combination of Ad-PUMA and irradiation significantly suppressed the cell growth,and increased the percentage of apoptotic cells than separate treatment.Irradiation induced PUMA expression in HeLa cell.Conclusions:Our data indicate that transfection of cervical cancer cells with Ad-PUMA is a potential novel approach to the therapy of HPV positive cervical cancer.