Effect of AQP9 Expression in Androgen-Independent Prostate Cancer Cell PC3.
Effect of AQP9 Expression in Androgen-Independent Prostate Cancer Cell PC3.
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AQP9 在雄激素非依赖性前列腺癌细胞 PC3 中表达的影响
DOI：
10.3390/ijms17050738
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发表时间：
2016-05-14
影响因子：
5.6
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Chen Q;Zhu L;Zheng B;Wang J;Song X;Zheng W;Wang L;Yang D;Wang J
前列腺中的水通道蛋白9 （aquaporin 9, AQP9）受到雄激素的严格上调，可能是几种癌症的新的治疗靶点，但AQP9是否在雄激素非依赖性前列腺癌的调控中发挥作用尚不清楚。本研究在前列腺癌及癌旁组织中检测AQP9；应用AQP9- sirna沉默雄激素非依赖型前列腺癌细胞PC3细胞系中的AQP9。采用Western blot和流式细胞术检测对照组和AQP9-siRNA组相关功能的变化。结果表明，AQP9在癌组织中的诱导作用明显高于癌旁组织。此外，在PC3雄激素非依赖性前列腺癌细胞中，AQP9的敲低可以提高前列腺癌细胞的增殖抑制率。此外，敲低AQP9导致Bcl-2表达显著降低，Bax和cleaved caspase 3表达显著升高，表明敲低AQP9促进前列腺癌细胞凋亡。通过伤口愈合实验和基质侵袭，我们提示AQP9的表达影响前列腺癌细胞的运动和侵袭。此外，为了探索该通路可能参与了AQP9介导的前列腺癌细胞的运动和侵袭，与对照细胞相比，转染AQP9 sirna的细胞中ERK1/2的磷酸化被显著抑制，这表明AQP9参与了雄激素非依赖性前列腺癌细胞中ERK通路的激活。
It is known that aquaporin 9 (AQP9) in the prostate was strictly upregulated by androgen and may represent a novel therapeutic target for several cancers, but whether AQP9 plays a role in the regulation of androgen-independent prostate cancer still remains unclear. In the present study, AQP9 was determined in prostate cancer and adjacent cancer tissues; AQP9-siRNA was applied to silencing AQP9 in androgen-independent prostate cancer cell PC3 cell line. Western blot and flow cytometry analysis were employed to detect changes in related-function of control and AQP9-siRNA groups. The results showed that AQP9 is significantly induced in cancer tissues than that in adjacent cancer tissues. Moreover, knockdown of AQP9 in PC3 androgen-independent prostate cancer cell prostate cancer cells increased inhibition rates of proliferation. In addition, knockdown of AQP9 resulted in a significant decrease in the expression of the Bcl-2 and with a notable increase in the expression of Bax and cleaved caspase 3, indicated that AQP9 knockdown promoted apoptosis in prostate cancer cells. From wound healing assay and matrigel invasion, we suggested that AQP9 expression affects the motility and invasiveness of prostate cancer cells. Moreover, In order to explore the pathway may be involved in AQP9-mediated motility and invasion of prostate cancer cells, the phosphorylation of ERK1/2 was significant suppressed in AQP9 siRNA-transfected cells compared with that in control cells, suggesting that AQP9 is involved in the activation of the ERK pathway in androgen-independent prostate cancer cells.