Synergistic gastric cancer inhibition by chemogenetherapy with recombinant human adenovirus p53 and epirubicin: an in vitro and in vivo study.
This study was designed to investigate the in vitro and in vivo antitumor effect on SGC-7901 gastric cancer cells by chemogenetherapy. SGC-7901 cells were treated by chemogenetherapy with Gendicine, a recombinant human Ad-p53 injection (rAd-p53), and epirubicin hydrochloride (EPI), a cytotoxic chemotherapy agent. Compared with blank control, rAd-p53, EPI, and combined therapy achieved SGC-7901 growth inhibition by 32.26, 35.48, 43.44%, respectively on day 1 and 70.62, 78.82, 87.15%, respectively on day 2 (rAd-p53, EPI VS control, p<0.01; rAd-p53+EPI VS either alone, p<0.05). Flow cytometry study confirmed that rAd-p53 and/or EPI mainly inhibit the cell cycle at S phase. SGC-7901 cells were subcutaneously injected into the nude mice to form xenograft models, which were treated with rAd-p53 and EPI. Compared with the blank control, treatment with rAd-p53 at the dose of 10 µl of 10(12) vp/ml and EPI at the dose of 1.25 mg/kg, 7 times in 3 weeks, resulted in 80 and 60% of tumor growth inhibition, respectively. No animal death was observed, although 2 nude mice in rAd-p53 group developed liver toxicity and 1 nude mouse in EPI group developed cardiac toxicity. rAd-p53 and EPI have synergistic tumor inhibition effect on gastric cancer cells.
Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.
Yi-Shan
YS
Xie
Yan-Hua
YH
Zhang
Shao-Ping
SP
Liu
Shi-Quan
SQ
Liu
Chun-Wei
CW
Peng
Long
L
Wu
He-Shen
HS
Luo
Yan
Y
Li
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics / Q000502:physiology; D000465:Algorithms; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004357:Drug Synergism; D015251:Epirubicin / Q000627:therapeutic use*; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008954:Models, Biological; D011994:Recombinant Proteins / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D015251:Epirubicin