重组人腺病毒 p53 与表柔比星联合化疗协同抑制胃癌：体外与体内研究。

Synergistic gastric cancer inhibition by chemogenetherapy with recombinant human adenovirus p53 and epirubicin: an in vitro and in vivo study.

机构信息

Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.

出版信息

Oncol Rep. 2010 Dec;24(6):1613-20.

Abstract

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.

摘要

本研究旨在通过化学基因治疗（chemogenetherapy）研究对 SGC-7901 胃癌细胞的体外和体内抗肿瘤作用。用重组人 Ad-p53 注射液（rAd-p53）、细胞毒性化疗药物盐酸表柔比星（EPI）对 SGC-7901 细胞进行化学基因治疗。与空白对照相比，rAd-p53、EPI 和联合治疗在第 1 天分别使 SGC-7901 细胞生长抑制率达到 32.26%、35.48%、43.44%，在第 2 天分别达到 70.62%、78.82%、87.15%（rAd-p53、EPI 与对照组相比，p<0.01；rAd-p53+EPI 与单独用药相比，p<0.05）。流式细胞术研究证实 rAd-p53 和/或 EPI 主要将细胞周期阻滞在 S 期。将 SGC-7901 细胞皮下注射到裸鼠体内形成异种移植模型，并用 rAd-p53 和 EPI 进行治疗。与空白对照组相比，rAd-p53 剂量为 10 µl 的 10(12) vp/ml 和 EPI 剂量为 1.25 mg/kg，每周 1 次，连续 7 次，肿瘤生长抑制率分别达到 80%和 60%。没有动物死亡，尽管 rAd-p53 组的 2 只裸鼠发生肝毒性，EPI 组的 1 只裸鼠发生心脏毒性。rAd-p53 和 EPI 对胃癌细胞具有协同的肿瘤抑制作用。