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目的:观察重组腺病毒TRAIL基因制剂联合抗EGFR靶向药物对H460肺癌细胞株及裸鼠移植瘤增殖的影响。方法:重组腺病毒TRAIL基因治疗制剂分别与EGFR信号通路靶向治疗药物Iressa、Tarceva、以及C225联合应用于H460肺腺癌细胞株,采用MTT法以及流式细胞仪检测不同用药方案的抗肿瘤作用;在裸鼠H460肺癌模型中验证重组腺病毒TRAIL制剂与C225的协同抗肿瘤作用。结果:在体外实验中发现Iressa和Tarceva可以增加重组腺病毒TRAIL基因制剂对H460肺癌细胞的抗肿瘤作用(P<0.05);重组腺病毒TRAIL基因制剂在体外实验中与C225并不存在协同效应(P>0.05),但在裸鼠H460肺癌模型中重组腺病毒TRAIL基因制剂与C225有明显的协同抗肿瘤作用(P<0.05)。结论:本研究初步探讨了基因治疗与靶向治疗的联合抗肿瘤作用,实验发现EGFR信号通路上的靶向治疗药物包括小分子酪氨酸激酶抑制剂以及EGFR单克隆抗体均可以增加重组腺病毒TRAIL基因制剂抗肺癌作用。
Objective: To observe the effect of recombinant adenovirus TRAIL gene preparation combined with anti-EGFR targeting agents on the proliferation of H460 lung cancer cell lines and xenografts in nude mice. Methods: The recombinant adenovirus TRAIL gene preparation was used in combination with Iressa, Tarceva, and C225, respectively, on H460 lung adenocarcinoma cell lines. MTT assay and flow cytometry were used to detect the anti-tumor effect of different regimens The synergistic antitumor effect of recombinant adenovirus TRAIL and C225 was verified in nude mice model of H460 lung cancer. Results: In vitro experiments showed that Iressa and Tarceva could increase the antitumor effect of recombinant adenovirus TRAIL gene on H460 lung cancer cells (P <0.05). The recombinant adenovirus TRAIL gene preparation had no synergistic effect with C225 in vitro P> 0.05). However, there was a significant synergistic antitumor effect between TRAIL gene preparation and C225 in nude mice H460 lung cancer model (P <0.05). CONCLUSIONS: In this study, the combined anti-tumor effect of gene therapy and targeted therapy was initially discussed. It was found that targeted therapeutic agents on the EGFR signaling pathway, including small molecule tyrosine kinase inhibitors and monoclonal antibodies against EGFR, can increase the effect of recombinant adenovirus TRAIL gene preparation against lung cancer.