Recombinant adenoviruses expressing TRAIL demonstrate antitumor effects on non-small cell lung cancer (NSCLC)
Recombinant adenoviruses expressing TRAIL demonstrate antitumor effects on non-small cell lung cancer (NSCLC)
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DOI：
10.1385/mo:23:2:191
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发表时间：
2006-01-01
期刊：
影响因子：
3.4
通讯作者：
Sun, M
中科院分区：
文献类型：
--
作者：
Yang, F;Shi, P;Sun, M
简介：肿瘤坏死因子相关凋亡诱导配体（tumor necrosis factor-related apoptosis-inducing ligand，TRAIL）可诱导多种恶性肿瘤细胞凋亡，但不诱导正常细胞凋亡。这种对异常细胞的优先毒性使TRAIL成为对抗癌症的非常强大的治疗武器。然而，需要大量的TRAIL来抑制体内肿瘤生长是阻碍其在临床上广泛应用的主要因素之一。为了克服这一点，我们构建了一种携带人全长TRAIL基因的复制缺陷型腺病毒（Ad-TRAIL），并测试其与重组可溶性TRAIL蛋白相比对肺癌模型系统的功效。为探讨腺病毒介导的肿瘤坏死因子相关凋亡诱导配体（Ad-TRAIL）对非小细胞肺癌（NSCLC）的抗肿瘤活性和治疗价值，以YTMLC、GLC、A549、和H460细胞。Western blotting和流式细胞术检测TRAIL蛋白表达。细胞增殖实验检测细胞活力，DNA梯状条带和细胞周期分析检测细胞凋亡。为了进一步评价Ad-TRAIL在体内的作用，将YTMLC细胞接种于裸鼠皮下。随后将Ad-TRAIL施用到建立的肿瘤中。结果：Ad-TRAIL感染YTMLC细胞后，细胞存活率下降，凋亡率升高。结论：TRAIL基因治疗为NSCLC的治疗提供了一种有前途的方法。
Introduction: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of malignant cells, but not in normal cells. This preferential toxicity to the abnormal cells renders TRAIL potentially a very powerful therapeutic weapon against cancer. However, a requirement for large quantities of TRAIL to suppress tumor growth in vivo is one of the major factors that has hindered it from being widely applied clinically. To overcome this, we constructed a replication-deficient adenovirus that carries a human full-length TRAIL gene (Ad-TRAIL) and tested its efficacy against a lung cancer model system in comparison to that of the recombinant soluble TRAIL protein.Methods: To investigate the antitumor activity and therapeutic value of the Ad-TRAIL on the non-small cell lung cancer (NSCLC), four NSCLC cell lines, namely, YTMLC, GLC, A549, and H460 cells, were used. TRAIL protein expression was determined by Western blotting and flow cytometry. Cell viability was analyzed by proliferation assay, and DNA ladder and cell-cycle analysis were used to identify apoptosis. To further evaluate the effect of Ad-TRAIL in vivo, YTMLC cells were inoculated to the subcutis of nude mice. The Ad-TRAIL was subsequently administered into the established tumors. Tumor growth and the TRAIL toxicity were evaluated after treatment.Results: YTMLC cells infected with Ad-TRAIL showed decreased cell viability and a higher percentage of apoptosis. Similar, Ad-TRAIL treatment also significantly suppressed tumor growth in vivo.Conclusions: TRAIL gene therapy provides a promising therapy for the treatment of NSCLC.