Mitomycin C and cisplatin enhanced the antitumor activity of p53-expressing adenovirus in cervical cancer cells.
This study investigated the enhanced antitumor activity of Ad5-p53 in combination with mitomycin C (MMC) or cisplatin (DDP) in cervical cancer cell lines SiHa and C-33A. MMC and DDP inhibited the growth of SiHa and C-33A cells in a dose-dependent manner, and the combination of MMC or DDP with Ad5-p53 showed a stronger growth inhibition than those treated with either Ad5-p53, MMC, or DDP alone. As evidenced by the formation of the approximately 200 bp DNA ladder and the appearance of sub-G1 peak, both MMC and DDP induced apoptosis in cervical cancer cells. Western blot analysis of p53 showed that MMC/DDP did not induce the increase of p53 protein in SiHa cells nor the increase of the cellular and nuclear p53 protein in Ad5-p53 transfected Saos-2 cells. Taken together, these results suggested that the combination of Ad5-p53 and MMC/DDP may serve as an effective therapeutic regime for human cervical cancer treatment.
Huang
T G
TG
Department of Obstetrics and Gynecology, University of Hong Kong, 6/F Professorial Block, Queen Mary Hospital, Pokfulam Road, Hong Kong, People's Republic of China.
Ip
S M
SM
Yeung
W S
WS
Ngan
H Y
HY
D000260:Adenoviruses, Human / Q000235:genetics*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D016158:Genes, p53; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology*; D012516:Osteosarcoma / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
D018906:Antineoplastic Agents, Alkylating; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D016685:Mitomycin; D002945:Cisplatin