摘要
目的 探讨p53重组腺病毒 (Ad p53)与顺铂 (CDDP)或三氧化二砷 (As2 O3)联合应用提高膀胱癌疗效的可能性及其机制。方法 将Ad p53[1 0 0感染强度 (MOI) ]与CDDP(0 .5mg/L)或As2 O3(2 .0 μmol/L)联合应用 ,通过细胞生长抑制实验、克隆形成实验、细胞周期分析、免疫组织化学分析以及裸鼠皮下移植瘤模型 ,观察其对膀胱癌EJ细胞的作用及机制。结果 与单独应用相比 ,Ad p53与低剂量的CDDP或As2 O3联合可明显抑制EJ细胞体外生长 ,诱导EJ细胞凋亡 ,EJ细胞G2 /M期阻滞更明显 ;裸鼠体内肿瘤发生时间延迟 ,4周后肿瘤体积与单独应用时相比 ,差异有显著性 (P <0 .0 5)。结论 基因治疗与化疗联合应用 。
Objective To investigate the possibility and mechanism of p53 expressing adenovirus combined with CDDP or As 2O 3 in improving the therapeutic effects of human bladder cancer cell line EJ.Methods The human bladder cancer cell line EJ was transfected with adenovirus mediated p53 gene (Ad p53),combined with administration of cisplatin (CDDP) or arsenic trioxide (As 2O 3).The cell growth,morphological changes,cell cycle, apoptosis and molecular changes were observed using methods of cell counting,reverse microscopy,flow cytometry,cloning formation test,RT PCR,immunocytochemical assays and in vivo experiments.Results Ad p53 transfer combined with low dose of CDDP (or As 2O 3) to EJ cells could exert substantially stronger therapeutic effects than the single agent treatment.Especially in in vivo experiments,combined administration of p53 and CDDP induced almost complete tumor remission as compared to the partial tumor remission induced by single agent.Moreover,delivery of Ad p53,or administration of minimal dose of CDDP or As 2O 3 or combined regimen could induce massive apoptosis of EJ cells.Cell cycle analysis demonstrated that administration of CDDP or As 2O 3 remarkably arrested EJ cell in G 2/M prior to apoptotic cell death.When treated with combined regimen,the cells were arrested in G 1 to a greater extent prior to apoptotic cell death.Conclusion After introduced into EJ cell,Ad p53 shows an enhanced therapeutic efficiency for EJ cell when combined with CDDP or As 2O 3.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2002年第3期225-226,共2页
Chinese Journal of Experimental Surgery
基金
国家863计划资助项目(Z200102)
