Increased therapeutic potential of an experimental anti-mitotic inhibitor SB715992 by genistein in PC-3 human prostate cancer cell line.
Increased therapeutic potential of an experimental anti-mitotic inhibitor SB715992 by genistein in PC-3 human prostate cancer cell line.
复制标题
在PC-3人前列腺癌细胞系中染料木黄酮的实验性抗溶酶抑制剂SB715992的治疗潜力增加。
DOI：
10.1186/1471-2407-6-22
复制
发表时间：
2006-01-24
期刊：
影响因子：
3.8
通讯作者：
Sarkar, FH
中科院分区：
文献类型：
--
作者：
Davis, DA;Sarkar, SH;Hussain, M;Li, YW;Sarkar, FH
驱动蛋白纺锤体蛋白（KSP）是在有丝分裂纺锤体形成中发挥重要作用的马达蛋白。HsEg 5是一种KSP，负责形成双极纺锤体，这对有丝分裂期间的适当细胞分裂至关重要。HsEg 5的功能为操纵细胞周期和诱导细胞凋亡提供了新的靶点。SB 715992是一种实验性KSP抑制剂，已被证明可以干扰双极纺锤体的形成，因此使其成为抗癌药物的优秀候选者。我们的主要目的是a）研究SB 715992对PC-3人前列腺癌细胞系的细胞生长抑制作用，B）研究SB 715992与染料木黄酮（一种天然存在的染料木黄酮）组合时是否可以增强SB 715992的生长抑制作用，以及c）确定基因表达谱以建立SB 715992作用的分子机制。PC-3细胞用不同浓度的SB 715992、30 μM染料木黄酮和SB 715992加30 μM染料木黄酮处理。处理后，PC-3细胞的细胞增殖，诱导凋亡，基因和蛋白质表达的改变，使用细胞抑制测定，凋亡测定，微阵列分析，实时RT-PCR和Western印迹分析。SB 715992抑制PC-3细胞增殖并诱导其凋亡。发现SB 715992调节与控制细胞增殖、细胞周期、细胞信号传导途径和凋亡相关的基因的表达。此外，我们的研究结果表明，SB 715992和染料木黄酮的组合治疗引起显着更大的细胞生长抑制和诱导细胞凋亡相比，任何一种药物单独的效果。我们的研究结果清楚地表明，SB 715992是一种有效的抗肿瘤剂，其治疗效果可以通过染料木黄酮增强。因此，我们认为，SB 715992可能是一种新的药物，用于治疗前列腺癌与更大的成功时，与无毒的天然药物如染料木素。
Kinesin spindle proteins (KSP) are motor proteins that play an essential role in mitotic spindle formation. HsEg5, a KSP, is responsible for the formation of the bipolar spindle, which is critical for proper cell division during mitosis. The function of HsEg5 provides a novel target for the manipulation of the cell cycle and the induction of apoptosis. SB715992, an experimental KSP inhibitor, has been shown to perturb bipolar spindle formation, thus making it an excellent candidate for anti-cancer agent. Our major objective was a) to investigate the cell growth inhibitory effects of SB715992 on PC-3 human prostate cancer cell line, b) to investigate whether the growth inhibitory effects of SB715992 could be enhanced when combined with genistein, a naturally occurring isoflavone and, c) to determine gene expression profile to establish molecular mechanism of action of SB715992. PC-3 cells were treated with varying concentration of SB715992, 30 μM of genistein, and SB715992 plus 30 μM of genistein. After treatments, PC-3 cells were assayed for cell proliferation, induction of apoptosis, and alteration in gene and protein expression using cell inhibition assay, apoptosis assay, microarray analysis, real-time RT-PCR, and Western Blot analysis. SB715992 inhibited cell proliferation and induced apoptosis in PC-3 cells. SB715992 was found to regulate the expression of genes related to the control of cell proliferation, cell cycle, cell signaling pathways, and apoptosis. In addition, our results showed that combination treatment with SB715992 and genistein caused significantly greater cell growth inhibition and induction of apoptosis compared to the effects of either agent alone. Our results clearly show that SB715992 is a potent anti-tumor agent whose therapeutic effects could be enhanced by genistein. Hence, we believe that SB715992 could be a novel agent for the treatment of prostate cancer with greater success when combined with a non-toxic natural agent like genistein.
登录
查看更多内容
影响因子：
8
作者：
Gong, LJ;Li, YW;Sarkar, FH
通讯作者：
Sarkar, FH
影响因子：
2.9
作者：
Li, YW;Ellis, KL;Sarkar, FH
通讯作者：
Sarkar, FH
影响因子：
2.9
作者：
DeBonis, S;Simorre, JP;Kozielski, F
通讯作者：
Kozielski, F
影响因子：
--
作者：
Haque, SA;Hasaka, TP;Baas, PW
通讯作者：
Baas, PW
影响因子：
11.2
作者：
Sakowicz, R;Finer, JT;Wood, KW
通讯作者：
Wood, KW