受体依赖性TRAIL重组腺病毒对人肺癌细胞凋亡的诱导作用

来源 :中国肿瘤生物治疗杂志 | 被引量 : 0次 | 上传用户:whsvlsy
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目的:观察重组TRAIL腺病毒(Ad5-TRAIL及Ad5F35-TRAIL)对人非小细胞肺癌(nonsmall-cell lung cancer,NSCLC)原代培养细胞和细胞株的凋亡诱导作用,探讨两种Ad-TRAIL用于肺癌基因治疗的价值。方法:采用流式细胞术检测人肺癌细胞系A549、Z793、QG56和NCI-H520及10例原代培养肺癌细胞中CAR和CD46的表达水平;分别以Ad5-TRAIL及Ad5F35-TRAIL重组腺病毒按MOI 10和50感染上述细胞,48 h后Annexin V-FITC双标法流式细胞术检测细胞的早期凋亡。结果:A549、Z793、QG56和NCI-H520 4株肺癌细胞中,CD46的表达均明显高于CAR表达。Z793、QG56细胞对Ad5-TRAIL和Ad5F35-TRAIL的作用较敏感,MOI=10感染后凋亡率分别为(11.76±2.10)%、(15.96±2.89)%和(6.05±1.58)%、(10.11±1.26)%,显著高于对照组[(2.33±0.37)%和(5.95±1.89)%,P<0.05];MOI=50感染时NCI-H520细胞凋亡率分别为(12.89±3.2)%和(9.08±1.35)%,与对照组(7.04±2.17)%相比差异无统计学意义(P>0.05);Ad5-TRAIL和Ad5F35-TRAIL均不能诱导A549细胞凋亡。10例原代肺癌细胞CD46表达也明显较CAR高;Ad5-TRAIL或Ad5F35-TRAIL感染后,5例的原代肺癌细胞检测到凋亡;与Ad5-TRAIL相比,Ad5F35-TRAIL诱导的凋亡率更高。结论:两种TRAIL重组腺病毒对非小细胞肺癌细胞均有凋亡诱导作用,Ad5F35-TRAIL的作用强于Ad5-TRAIL,更适合于非小细胞肺癌的基因治疗。 OBJECTIVE: To observe the apoptosis-inducing effects of recombinant TRAIL adenovirus (Ad5-TRAIL and Ad5F35-TRAIL) on primary cultured human non-small cell lung cancer (NSCLC) The value of gene therapy for lung cancer. Methods: The expression of CAR and CD46 in A549, Z793, QG56 and NCI-H520 human lung cancer cell lines and 10 primary lung cancer cells were detected by flow cytometry. The expression of CAR and CD46 were detected by Ad5-TRAIL and Ad5F35-TRAIL recombinant adenovirus The above cells were infected with MOI 10 and 50, and the cells were pre-treated with Annexin V-FITC double-labeled flow cytometry after 48 h. Results: The expression of CD46 in A549, Z793, QG56 and NCI-H520 lung cancer cells was significantly higher than that in CAR. The apoptosis rates of Z793 and QG56 cells were more sensitive to Ad5-TRAIL and Ad5F35-TRAIL than that of Ad5F35-TRAIL group (P <0.05). The apoptotic rates of Z793 and QG56 cells were (11.76 ± 2.10)%, (15.96 ± 2.89)% and (6.05 ± 1.58)%, (1.33 ± 0.37)% and (5.95 ± 1.89)% respectively, P <0.05]. The apoptosis rates of NCI-H520 cells at the MOI = 50 infection were (12.89 ± 3.2)% (9.08 ± 1.35)%, respectively. There was no significant difference between the two groups (P> 0.05). Ad5-TRAIL and Ad5F35-TRAIL could not induce A549 cell apoptosis. The expression of CD46 in 10 primary lung cancer cells was also significantly higher than that of CAR. Apoptosis was detected in 5 cases of primary lung cancer cells after Ad5-TRAIL or Ad5F35-TRAIL infection. Compared with Ad5-TRAIL, apoptosis induced by Ad5F35-TRAIL Higher rates. Conclusion: Both TRAIL recombinant adenovirus can induce apoptosis in non-small cell lung cancer cells. The effect of Ad5F35-TRAIL is stronger than Ad5-TRAIL, which is more suitable for gene therapy of non-small cell lung cancer.
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