| 庄 莉 董 超 杨润祥 高春林.抑制 Livin 基因对肺腺癌 SPC-A1 细胞增殖及顺铂敏感性的影响[J].,2015,15(6):1036-1040 |
| 抑制 Livin 基因对肺腺癌 SPC-A1 细胞增殖及顺铂敏感性的影响 |
| Inhibition of Livin Expression Suppresses Cell Proliferation and Enhances theChemosensitivity to Cisplatin in Human Lung Adenocarcinoma Cells |
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| DOI： |
| 中文关键词: Livin RNA 干扰 Flavopiridol TRAIL 顺铂 SPC-A1 |
| 英文关键词: Livin RNA interference Flavopiridol TRAIL Cisplatin SPC-A1 |
| 基金项目:云南省科技厅应用基础研究基金计划面上项目（ 201 0ZC131） |
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| 中文摘要: |
| 目的： Livin 是近年来发现的人类凋亡抑制 蛋白（ inhibitorof apoptosis protein, IAP）家族的新成员 ， 发现在多 数肿瘤中表达,与
肿瘤发生有密切关系 ,并可能作为肿瘤诱导凋亡治疗的新靶点。 本研究旨在探讨 siRNA-Livin 和夫拉平度（ Flavopiridol， FP）协同 凋
亡诱导配体（ TRAIL）两种方式有效抑制 Livin 表达，诱导非小细胞肺癌 SPC-A1 凋亡并增强对化疗药物顺铂的敏感性。 方法：
siRNA-Livin 转染 SPC-A1， Real-Time PCR 检测 Livin 基因的表达水平， MTT 检测干扰组和干扰加药组肿瘤细胞的 增殖及活性；
TRAIL
、 FP 单独及联合作用诱导细胞凋亡， 蛋白质印迹法检测凋亡抑制 蛋白 Livin 的表达水平， MTT 检测各处理组细胞的增殖及
活性。 结果： 100 nmol/LFP 处理组（ F）细胞存活率为（ 84.30± 1 .34）%， 1 00 ng/mLTRAIL 处理组（ T）为（ 93.40± 1.56）%， FP 和 TRAIL
联合组 （ F+T） 为 （ 48.02± 1 .35）%， siRNA-Livin 处理组为 （ 50.88 ± 1 .14） %， 1 .2 滋g/mL Cisplatin 处理组为 （ 19.30± 0.89）%，
siRNA-livin+Cisplatin 组为（ 1 4.37± 0.81）%， FP+T+Cisplatin 组为（ 1 0.86± 0.87）%， C 组存活率为 1 00 %。 F+T 组对细胞的增殖抑制
作用显著高于单独用 药组， siRNA-livin+Cisplatin 与 siRNA-Livin 组相比、 FP+T+Cisplatin 与 FP+T 组相比都显著增强了化疗药物
对 SPC-A1 的杀伤作用。 50 滋mol/LZ-VAD-FMK 预处理后联合用 药组细胞的存活率为（ 88.16± 1.64）%， caspase 抑制 剂 能明 显抑
制 F+T 联合处理组的凋 亡效应。 结论： RNA 干扰和 F+T 联合用 药都能显著降低凋亡抑制蛋白 Livin 的表达，有效抑制肿瘤细胞的
增殖生长， 并增强肿瘤细胞对化疗药物顺铂的敏感性，为肺腺癌的靶向治疗提供新的理论依据。 |
| 英文摘要: |
| Objective:Livin is a novel member of the inhibitor of apoptosis protein (IAP) family that has been reported to be
overexpressed in a variety of human malignancies. In order to investigate how depletion of Livin affects the proliferation of human lung
adenocarcinoma cells, we used two quite different ways to down-regulate the livin expression, including RNAi-based approach
specifically targeting Livin mRNA and the synergistic inhibitory effect between Flavopiridol and TRAIL.Methods:The siRNA
recombinant expression vectors targeting Livin gene were transfected into SPC-A1 cells with Lipofectamine 2000. Real-time PCR was
used to detect the expression of Livin mRNA. And the cell proliferation and viability was measured by MTT assay. The apoptosis
inhibitory effect of Flavopiridol and TRAIL used singly and combinedly was also studied in SPC-A1 . Western blotting analysis was used
to confirm the expression of Livin protein. Cell proliferation and viability was tested by MTT assay.Results:The survival rate of each
group was showed as follows: the Flavopiridol treatment group was (84.30± 1 .34) %, the TRAIL treatment was (93.40± 1.56) %, the FP
and TRAIL combination treatment group was (48.02± 1 .35) %, the siRNA-Livin treatment group was (50.88± 1 .1 4) %, the Cisplatin
treatment group was (19.30± 0.89)%, the siRNA-livin and Cisplatin combination group was (1 4.37± 0.81) %, the FP and TRAIL and
Cisplatin combination group was (1 0.86 ± 0.87) % , the Caspase inhibitor Z-VAD-FMK treatment group was (88.16 ± 1.64) % , the
negative control group was 100 %. The survival rate of FP and TRAIL combination group was much lower than the FP group and TRAIL
goup.Conclusion:Both the RNA interference and FT synergistic could obviously inhibited the expression of Livin, effectively decreased
the proliferation of SPC-A1 cells, and promoted the sensitivity of chemotherapeutic medicine cisplatin. All of this provide new theoretical
foundation for the targeted therapy of lung cancer. |
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