Adenovirus-mediated p21((WAF1/SDII/CIP1)) gene transfer induces apoptosis of human cervical cancer cell lines

p21((WAF1/SDII/CIP1)) (p21) arrests cell growth by inhibiting cyclin-depend kinases. To explore the potential of using p21 for the gene therapy of cer vical cancer, we infected human papillomavirus (HPV)-positive cervical canc er cells (HeLa, SiHa, and Z172) and HPV-negative cervical cancer cells (C33 A) with recombinant adenovirus encoding p21 cDNA. The results revealed that effective inhibition of cell growth could be achieved by sense p21 adenovi rus but not antisense p21 adenovirus infection and occurred through apoptos is as measured by DNA fragmentation and chromatin condensation. Apoptosis w as also observed in xenografts of human cervical cancer cells infected with sense p21 adenovirus, as confirmed by in situ terminal deoxynucleotidyl-tr ansferase-mediated dUTP-biotin nick end labeling (TUNEL). The apoptosis was not prevented by overexpression of the bcL-2 transgene. To sum up, the apo ptotic effect suggests that p21 should be a tumoricidal agent instead of a tumoristatic agent in preventing cervical cancers. In addition, our report substantiates the combination of the high efficiency of adenovirus vector-m ediated gene delivery and the apoptotic effect of p21.