Rho-Associated Protein Kinase (ROCK) Promotes Proliferation and Migration of PC-3 and DU145 Prostate Cancer Cells by Targeting LIM Kinase 1 (LIMK1) and Matrix Metalloproteinase-2 (MMP-2)

Rho-Associated Protein Kinase (ROCK) Promotes Proliferation and Migration of PC-3 and DU145 Prostate Cancer Cells by Targeting LIM Kinase 1 (LIMK1) and Matrix Metalloproteinase-2 (MMP-2)
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DOI:
10.12659/msm.912098
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发表时间:
2019-04-26
影响因子:
3.1
通讯作者:
Chen, Weihua
Chen, Weihua
中科院分区:
医学4区
文献类型:
--
作者:
Gong, Hua;Zhou, Lan;Chen, Weihua

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背景:在前列腺癌的发生和发展过程中,细胞的增殖和迁移导致肿瘤的侵袭和转移,与患者的发病率和死亡率有关。Rho相关蛋白激酶(ROCK)此前已被证明在前列腺癌中上调,但其生物学作用仍知之甚少。本研究旨在研究ROCK在前列腺癌PC-3和DU145细胞增殖和迁移中的作用,并通过下调ROCK1和ROCK2的RNA表达来确定可能的靶点。材料/方法:采用RNA干扰(RNAi)技术沉默PC-3和DU145细胞中ROCK1和ROCK2的表达。细胞也用一种特殊的ROCK抑制剂Y27632处理。采用细胞计数试剂盒-8(CCK-8)法检测前列腺癌细胞的增殖率,并进行细胞迁移和侵袭实验。结果:在PC-3和DU145前列腺癌细胞中,ROCK1和ROCK2基因的敲除降低了细胞的迁移和侵袭能力。ROCK1和ROCK2调控PC-3和DU145前列腺癌细胞的增殖。结论:在PC-3和DU145细胞中,ROCK通过靶向LIMK1和MMP2促进细胞的增殖和迁移。
Background: In the pathogenesis and progression of prostate cancer, cell proliferation and cell migration results in tumor invasion and metastasis that is associated with patient morbidity and mortality. Rho-associated protein kinase (ROCK) has previously been shown to be upregulated in prostate cancer, but its biological role remains poorly understood. This study aimed to investigate the role of ROCK in the proliferation and migration of PC-3 and DU145 prostate cancer cells and to identify the possible targets involved by knockdown of ROCK1 and ROCK2 RNA expression.Material/Methods: An RNA interference (RNAi) assay was performed to silence the expression of ROCK1 and ROCK2 in the PC-3 and DU145 human prostate cancer cell lines. Cells were also treated with a specific ROCK inhibitor, Y27632. A cell counting kit-8 (CCK-8) assay was used to determine the proliferation rate of prostate cancer cells, and cell migration and invasion assays were performed. Western blot and polymerase chain reaction were used to measure protein and RNA expression levels.Results: In PC-3 and DU145 prostate cancer cells, knockdown of ROCK1 and ROCK2 reduced cell migration and invasion. ROCK1 and ROCK2 regulated cell proliferation in PC-3 and DU145 prostate cancer cells. Protein levels of phosphorylated LIM kinase 1 (p-LIMK1) and matrix metalloproteinase-2 (MMP-2) were reduced in ROCK1 and ROCK2 siRNA transfected cells.Conclusions: In PC-3 and DU145 human prostate cancer cells, ROCK promoted cell proliferation and migration by targeting LIMK1 and MMP-2.