Anticancer activity of Noscapine, an opioid alkaloid in combination with Cisplatin in human non-small cell lung cancer.
Anticancer activity of Noscapine, an opioid alkaloid in combination with Cisplatin in human non-small cell lung cancer.
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DOI：
10.1016/j.lungcan.2010.06.002
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发表时间：
2011-03
期刊：
影响因子：
5.3
通讯作者：
Singh, Mandip
中科院分区：
文献类型：
--
作者：
Chougule, Mahavir;Patel, Apurva R.;Sachdeva, Pratik;Jackson, Tanise;Singh, Mandip
本研究的目的是检查诺斯卡品（Nos）和顺铂（Cis）联合治疗体外A549和H460肺癌细胞、体内小鼠异种移植模型的功效并研究潜在的机制。组合指数值（<0.6）表明Nos + Cis的协同作用，并且与用任一药剂处理相比，导致凋亡NSCLC细胞百分比的最高增加和p53、p21、半胱天冬酶3、裂解的半胱天冬酶3、裂解的PARP、Bax的表达增加，以及Bcl 2和存活蛋白的表达降低。在小鼠异种移植肺癌模型中，Nos + Cis治疗使肿瘤体积减少78.1 ± 7.5%，而单独Cis治疗使肿瘤体积减少38.2 ± 6.8%或Nos治疗使肿瘤体积减少35.4 ± 6.9%。与单药治疗组和对照组相比，Nos + Cis治疗降低了pAkt、Akt、细胞周期蛋白D1、存活素、PARP、Bcl 2的表达，并增加了p53、p21、Bax、裂解的PARP、半胱天冬酶3、裂解的半胱天冬酶3、裂解的半胱天冬酶8、半胱天冬酶8、裂解的半胱天冬酶9和半胱天冬酶9的表达。我们的研究结果表明，一氧化氮通过激活包括细胞凋亡在内的多个信号通路，以相加到协同的方式增强了顺式异构体的抗癌活性。这些发现表明使用Nos和Cis组合治疗肺癌的潜在益处。
The purpose of this study was to examine the efficacy of Noscapine (Nos) and Cisplatin (Cis) combination treatment in vitro in A549 and H460 lung cancer cells, in vivo in murine xenograft model and to investigate the underlying mechanism. The combination index values (<0.6) suggested synergistic effects of Nos + Cis and resulted in the highest increase in percentage of apoptotic NSCLC cells and increased expression of p53, p21, caspase 3, cleaved caspase 3, cleaved PARP, Bax, and decreased expression of Bcl2 and surviving proteins compared with treatment with either agent. Nos + Cis treatment reduced tumor volume by 78.1 ± 7.5% compared with 38.2 ± 6.8% by Cis or 35.4 ± 6.9% by Nos alone in murine xenograft lung cancer model. Nos + Cis treatment decreased expression of pAkt, Akt, cyclin D1, survivin, PARP, Bcl2, and increased expression of p53, p21, Bax, cleaved PARP, caspase 3, cleaved caspase 3, cleaved caspase 8, caspase 8, cleaved caspase 9 and caspase 9 compared to single-agent treated and control groups. Our results suggest that Nos enhanced the anticancer activity of Cis in an additive to synergistic manner by activating multiple signaling pathways including apoptosis. These findings suggest potential benefit for use of Nos and Cis combination in treatment of lung cancer.
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