Effects of lysophosphatidic acid on human colon cancer cells and its mechanisms of action

Effects of lysophosphatidic acid on human colon cancer cells and its mechanisms of action
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溶血磷脂酸对人结肠癌细胞的影响及其作用机制。

DOI:
10.3748/wjg.15.4547
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发表时间:
2009-09-28
影响因子:
4.3
通讯作者:
Pan, Bo-Rong
Pan, Bo-Rong
中科院分区:
医学2区
文献类型:
--
作者:
Sun, Hong;Ren, Juan;Pan, Bo-Rong

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目的:研究溶血磷脂酸(LPA)对人结肠癌细胞株SW480增殖、粘附、迁移和凋亡的影响及其作用机制。方法:采用甲基四唑法检测细胞增殖能力。采用流式细胞术检测细胞凋亡。使用Boyden transwell迁移室测量细胞迁移。根据实验方案在96孔板中进行细胞粘附测定。结果:与对照组相比,LPA以剂量依赖性和时间依赖性方式显着刺激SW480细胞增殖(P < 0.05),而丝裂原激活蛋白激酶(MAPK)抑制剂PD98059显着阻断LPA对增殖的刺激作用。 LPA还以剂量依赖性方式显着刺激SW480细胞的粘附和迁移(P < 0.05)。 Rho激酶抑制剂Y-27632显着抑制LPA对粘附和迁移的上调作用(P < 0.05)。 LPA显着保护细胞免受化疗药物顺铂和5-FU诱导的细胞凋亡(P < 0.05),但磷酸肌醇3激酶(PI3K)抑制剂LY294002显着阻断LPA对细胞凋亡的保护作用。结论:LPA刺激SW480细胞的增殖、粘附和迁移,并防止细胞凋亡。 Ras/Raf-MAPK、G12/13-Rho-RhoA 和 PI3K-AKT/PKB 信号通路可能参与其中。 (C) 2009 WJG 出版社和百事登。版权所有。
AIM: To study the effects of lysophosphatidic acid (LPA) on proliferation, adhesion, migration, and apoptosis in the human colon cancer cell line, SW480, and its mechanisms of action.METHODS: Methyl tetrazolium assay was used to assess cell proliferation. Flow cytometry was employed to detect cell apoptosis. Cell migration was measured by using a Boyden transwell migration chamber. Cell adhesion assay was performed in 96-well plates according to protocol.RESULTS: LPA significantly stimulated SW480 cell proliferation in a dose-dependent and time-dependent manner compared with the control group (P < 0.05) while the mitogen-activated protein kinase (MAPK) inhibitor, PD98059, significantly blocked the LPA stimulation effect on proliferation. LPA also significantly stimulated adhesion and migration of SW480 cells in a dose-dependent manner (P < 0.05). Rho kinase inhibitor, Y-27632, significantly inhibited the up-regulatory effect of LPA on adhesion and migration (P < 0.05). LPA significantly protected cells from apoptosis induced by the chemotherapeutic drugs, cisplatin and 5-FU (P < 0.05), but the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, significantly blocked the protective effect of LPA on apoptosis.CONCLUSION: LPA stimulated proliferation, adhesion, migration of SW480 cells, and protected from apoptosis. The Ras/Raf-MAPK, G12/13-Rho-RhoA and PI3K-AKT/PKB signal pathways may be involved. (C) 2009 The WJG Press and Baishideng. All rights reserved.