Adenovirus-mediated E2F-1 gene transfer in nonsmall-cell lung cancer induces cell growth arrest and apoptosis
Adenovirus-mediated E2F-1 gene transfer in nonsmall-cell lung cancer induces cell growth arrest and apoptosis
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DOI：
10.1183/09031936.02.00294502
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发表时间：
2002-09-01
影响因子：
24.3
通讯作者：
Wolff, G
中科院分区：
文献类型：
--
作者：
Kuhn, H;Liebers, U;Wolff, G
由于E2 F-1的过表达已被证明可诱导细胞凋亡，因此研究了腺病毒介导的E2 F-1转移在非小细胞肺癌细胞系中抑制肿瘤生长的能力。通过台盼蓝拒染法测定细胞增殖和活力。流式细胞术和多聚腺苷二磷酸核糖聚合酶裂解试验检测细胞凋亡诱导作用。在体内，E2 F-1对严重联合免疫缺陷（SCID）小鼠肿瘤生长的影响进行了测定。目前的实验表明，E2 F-1的过表达抑制肿瘤细胞的生长。Ade 2F感染后96 h凋亡细胞数量显著增加。抑制细胞生长和诱导细胞凋亡不依赖于基因组状态。Ade 2F治疗SCID小鼠移植性肿瘤可抑制肿瘤生长，提示腺病毒介导的E2 F-1基因治疗对非小细胞肺癌可能有效。
Since overexpression of E2F-1 has been shown to induce apoptosis, the ability of adenovirus-mediated transfer of E2F-1 to inhibit tumour growth in nonsmall-cell lung cancer cell lines was investigated.Three cell lines with various genomic status were infected with Ade2F. Cell proliferation and viability were determined by trypan blue exclusion. Apoptosis induction was assessed by flow cytometry and poly-adenosine diphosphate-ribose-polymerase cleavage assay. In vivo, the effect of E2F-1 on tumour growth was determined in severe combined immunodeficiency (SCID) mice.The current experiments showed that overexpression of E2F-1 suppressed tumour cell growth. The population of apoptotic cells was dramatically increased 96 h after infection with Ade2F. Inhibition of cell growth and induction of apoptosis was not dependent on genomic status. Moreover, treatment of implanted tumours in SCID mice with Ade2F inhibited tumour growth.These data suggest that adenovirus-mediated E2F-1 gene therapy may be effective in the treatment of nonsmall-cell lung cancer.