S29 ribosomal protein induces apoptosis in H520 cells and sensitizes them to chemotherapy
S29 ribosomal protein induces apoptosis in H520 cells and sensitizes them to chemotherapy
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DOI：
10.1016/s0006-291x(03)00532-1
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发表时间：
2003-04-25
影响因子：
3.1
通讯作者：
Singh, N
中科院分区：
文献类型：
--
作者：
Khanna, N;Sen, S;Singh, N
非小细胞肺癌（NSCLC）是最常见的肺癌类型，尤其是在印度，并显示出对抗癌治疗的耐药性。在我们早期的研究中，我们已经从诱导经历凋亡的大鼠胸腺细胞中分离了一个cDNA克隆，发现其编码S29核糖体蛋白[Biochem. Biophys.通信资源277（2000）476]。本研究旨在探讨S29 cDNA的高表达对NSCLC H520细胞的杀伤作用。我们发现，S29诱导细胞凋亡，增强抗癌药物的作用。分析了几种凋亡分子决定因子的表达，以了解S29诱导细胞凋亡的机制。我们观察到凋亡抑制蛋白（IAP）Bcl-2，Bcl-X-L和生存素的表达下调，促凋亡p53和Bax的上调，通过Western印迹法进行评估。还观察到线粒体释放细胞色素c和激活起始剂caspase-8和-9和效应剂caspase-3，随后裂解核底物聚（ADP-核糖）聚合酶。通过Δ Psi（m）的变化确定的渗透性转变不是细胞色素c释放的必要条件。凋亡诱导因子（AIF）的释放略有增加，NF-κ B依赖性转录活性降低。钙和端粒酶活性（增殖标记物）不参与。(C)2003 Elsevier Science（美国）。All rights reserved.
Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer especially in India and displays resistance to anticancer treatment. In our earlier study we had isolated a cDNA clone from rat thymocytes induced to undergo apoptosis, which was found to encode S29 ribosomal protein [Biochem. Biophys. Res. Commun. 277 (2000) 476]. In the present study an attempt has been made to find out whether enhanced expression of S29 cDNA can kill NSCLC H520 cells. We found that S29 induced apoptosis and augmented the effect of anticancer drugs. Expressions of several molecular determinants of apoptosis were analyzed in order to understand the mechanism of apoptosis induced by S29. We observed downregulation of the expression of inhibitors of apoptosis proteins (IAPs) Bcl-2, Bcl-X-L, and survivin and upregulation of pro-apoptotic p53 and Bax as assessed by Western blotting. Mitochondrial release of cytochrome c and activation of initiator caspase-8 and -9 and effector caspase-3, followed by cleavage of nuclear substrate poly(ADP-ribose) polymerase, were also observed. Permeability transition as determined by changes in DeltaPsi(m) was not a requirement for cytochrome c release. There was a marginal increase in the release of apoptosis inducing factor (AIF) and reduction of NF-kappaB dependent transcriptional activity. There was non-involvement of calcium and the telomerase activity, a proliferation marker. (C) 2003 Elsevier Science (USA). All rights reserved.