基因治疗与化疗联合应用对人肺腺癌GLC-82细胞作用的实验研究

目的 探讨基因治疗和化疗联合应用提高肿瘤疗效的可能性和初步机制。方法 将重组腺病毒载体（Ａｄ）介导的ｐ５３基因（Ａｄ－ｐ５３）与化疗药顺铂（ＣＤＤＰ）或三氧化二砷（Ａｓ２Ｏ３）联合，通过细胞生长和存活的抑制实验，流式细胞分析，末端转移酶介导的ｄＵＴＰ缺口末端标记检测，逆转录－聚合酶链反应，免疫组织化学检测，以及裸鼠皮下移植瘤模型的治疗实验，观察其对人肺腺癌ＧＬＣ－８２细胞的作用及可能机制。结果 Ａ

Experimental study on combination of Ad-p53 with CDDP or As_2O_3 in human lung adenocarcinoma cell line GLC-82

Objective To evaluate the therapeutic efficiency of combining p53 expressing adenovirus with chemotherapy agents on GLC 82 human lung adenocarcinoma cells. Methods Human lung adenocarcinoma cell line GLC 82 was transfected with adenovirus mediated p53 gene (Ad p53) combining with administration of either kind of chemotherapeutic agents cisplatin (CDDP) and arsenic trioxide (As 2O 3). The cell growth, morphological changes, cell cycle, apoptosis and molecular changes were measured using cell counting, reversmicroscope, flow cytometry, TUNEL, RT PC, immunocytochemical assays, and in vivo therapy experiments to evaluate the therapeutic efficiency of such combined regimen. Results Ad p53 transfer and CDDP (or As 2O 3) administration to GLC 82 cells could exertubstantially stronger therapeutic effects than the single agent treatment. Especially in in vivo experiments, combined administration of Ad p53 and CDDP induced almost complete tumor remission (89.0%) compared to the partial tumor remission induced by single agent (43.9% or 57.3%). Moreover, delivery of Ad p53, or administration of minimal dose CDDP or As 2O 3 or combined regimen could induce massive apoptosis of GLC 82 cells. Cell cycle analysis demonstrated that administration of CDDP or As 2O 3 remarkably arrested GLC 82 cells in G 2/M prior to apoptotic cell death. When treated with combined regimen, cells were arrested in G 2/M to a greater extent prior to apoptotic cell death. Conclusion After introduced into GLC 82 cells, Ad p53 shows enhanced therapeutic efficiency for GLC 82 cells when combined with CDDP or As 2O 3.