Novel combination therapy for human colon cancer with adenovirus-mediated wild-type p53 gene transfer and DNA-damaging chemotherapeutic agent.

摘要: Alteration of the wild-type (wt) p53 gene by mutation, deletion or re-arrangement is a major factor in development human colon cancer. Recent studies have demonstrated that might be an essential component apoptotic pathway triggered DNA-damaging stimuli such as chemotherapeutic agents and ionizing radiation. We examined anti-tumor effects adenovirus-mediated wt-p53 transfer combination with drug on cancer cell line WiDr, which homozygous for mutation gene. Treatment cisplatin following infection replication-deficient, recombinant adenoviral vector expressing (termed AdCMVp53) significantly suppressed growth WiDr cells compared to single treatments alone. To evaluate vivo efficacy AdCMVp53 given sequentially, were inoculated s.c. nu/nu mice. After 3 days, was injected into area where tumor implanted, followed i.p. administration cisplatin. Analysis initial inhibition at 21 days profound therapeutic cooperativity, though either alone only slowing growth. Our results suggest therapy using wt-p53-expressing adenovirus could useful strategy treating