Kuhar Meenakshi, Sen Sudip, Singh Neeta
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Anticancer Res. 2006 Mar-Apr;26(2A):1297-303.
Dietary phytochemicals have been shown to be chemopreventive against various types of cancer. This study was designed to investigate the enhancement of the chemoresponse to cisplatin by quercetin in human lung cancer H-520 cells and to elucidate the role of mitochondria in the induction of apoptosis. Apoptosis was detected by flow cytometry. The protein expressions of Bcl-XL, Bcl-2, Bax, cytochrome c and AIF were studied by Western blotting. The transcription of antioxidant enzymes was quantitated by RT-PCR. The findings suggested that priming H-520 cells with quercetin increased the cisplatin-induced apoptosis by 30.2%. This was accompanied by down-regulation of Bcl-XL and Bcl-2 and up-regulation of Bax. Both cytochrome c and AIF were implicated in the apoptotic process. There was no significant change in the transcription level of antioxidant enzymes in quercetin-mediated apoptosis. Based on these findings, it can be concluded that quercetin might act as an effective chemosensitizer in the chemotherapy of lung cancer by regulating the expression of various apoptosis-related genes.
膳食植物化学物质已被证明对多种类型的癌症具有化学预防作用。本研究旨在探讨槲皮素对人肺癌H-520细胞顺铂化疗反应的增强作用,并阐明线粒体在诱导细胞凋亡中的作用。通过流式细胞术检测细胞凋亡。采用蛋白质免疫印迹法研究Bcl-XL、Bcl-2、Bax、细胞色素c和凋亡诱导因子(AIF)的蛋白表达。通过逆转录聚合酶链反应(RT-PCR)对抗氧化酶的转录进行定量分析。研究结果表明,用槲皮素预处理H-520细胞可使顺铂诱导的细胞凋亡增加30.2%。这伴随着Bcl-XL和Bcl-2的下调以及Bax的上调。细胞色素c和AIF均参与了凋亡过程。在槲皮素介导的细胞凋亡中,抗氧化酶的转录水平没有显著变化。基于这些发现,可以得出结论,槲皮素可能通过调节各种凋亡相关基因的表达,在肺癌化疗中作为一种有效的化学增敏剂。