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400016 重庆,重庆医科大学附属第一医院泌尿外科
[ 任轲,E-mail: renke_rk@163.com REN Ke, E-mail: renke_rk@163.com
收稿:2018-09-21,
修回:2018-10-24,
纸质出版:2019-02-28
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任轲, 苟欣, 康简. Pim-2抑制前列腺癌细胞凋亡信号通路的研究[J]. 第三军医大学学报, 2019,41(4):323-330.
Ke REN, Xin GOU, Jian KANG. Pim-2 signal pathway inhibits apoptosis of prostate cancer cells[J]. Journal of Third Military Medical University, 2019, 41(4): 323-330.
任轲, 苟欣, 康简. Pim-2抑制前列腺癌细胞凋亡信号通路的研究[J]. 第三军医大学学报, 2019,41(4):323-330. DOI: 10.16016/j.1000-5404.201809151.
Ke REN, Xin GOU, Jian KANG. Pim-2 signal pathway inhibits apoptosis of prostate cancer cells[J]. Journal of Third Military Medical University, 2019, 41(4): 323-330. DOI: 10.16016/j.1000-5404.201809151.
目的
2
探讨癌基因Pim-2抑制前列腺癌细胞凋亡的机制及其信号通路。
方法
2
分别检测前列腺癌组织及前列腺增生组织中Pim-2及其下游信号通路因子的表达,通过RNAi技术分别沉默前列腺癌细胞株中Pim-2或XIAP表达,通过基因转染技术增强非肿瘤性前列腺上皮细胞中Pim-2或XIAP表达,检测eIF4B磷酸化水平及XIAP表达水平,测定细胞凋亡率。
结果
2
Pim-2在前列腺癌组织及细胞株中的表达显著高于前列腺增生组织及非肿瘤性前列腺细胞株(
P
<
0.05);在非肿瘤性前列腺细胞株中转染Pim-2后,其Pim-2表达水平显著增高,eIF4B磷酸化水平及XIAP表达水平也同时显著增高,而细胞凋亡率则显著降低(
P
<
0.05);在前列腺癌细胞株中转染Pim-2 SiRNA后,Pim-2表达水平显著减低,eIF4B磷酸化水平及XIAP表达水平也同时显著降低,而细胞凋亡率则显著增高(
P
<
0.05);在高表达Pim-2及XIAP的前列腺癌细胞株中转染XIAP SiRNA沉默其表达后,细胞凋亡率显著增高(
P
<
0.05);在低表达Pim-2及XIAP的非肿瘤性前列腺细胞株中转染XIAP增强其表达后,细胞凋亡率无明显变化。
结论
2
Pim-2在前列腺癌细胞中异常高表达;Pim-2可通过磷酸化eIF4B促进XIAP表达,抑制细胞凋亡;仅当Pim-2与XIAP同时高表达时才能抑制前列腺癌细胞凋亡。
Objective
2
To explore the mechanism by which Pim-2 signal pathway inhibits apoptosis of prostate cancer cells.
Methods
2
We examined the expression levels of Pim-2 and the downstream factors in prostate cancer tissues
benign prostatic hyperplasia tissues
prostate cancer cell lines and prostatic epithelial cells. In prostate cancer DU-145 cell line with Pim-2 or XIAP silencing using RNA interference technique and in non-neoplastic prostatic epithelial cell line RWPE-1 over-expressing Pim-2 or XIAP
via
gene transfection
we detected the phosphorylation level of eIF4B and the expression of XIAP and examined the apoptosis rate of the cells.
Results
2
Pim-2 was significantly over-expressed in prostate cancer tissues and prostate cancer cell lines as compared with benign prostatic hyperplasia tissue and non-neoplastic prostatic epithelial cells. RWPE-1 cells over-expressing Pim-2 showed significantly increased phosphorylation level of eIF4B with enhanced XIAP expression and a significantly lowered apoptosis rate. DU-145 cells with Pim-2 silencing exhibited significantly lowered phosphorylation level of eIF4B and XIAP expression with obviously increased cell apoptosis rate. XIAP silencing in DU-145 cells that over-expressed Pim-2 and XIAP caused a significant increase in the cell apoptosis rate; XIAP over-expression in RWPE-1 cells with low expressions of Pim-2 and XIAP did not cause significant changes in the cell apoptosis rate.
Conclusion
2
Pim-2 is over-expressed in prostate cancer cells. Pim-2 may inhibit the apoptosis of prostate cancer cells through phosphorylating eIF4B to promote XIAP expression
and this inhibitory effect occurs only when both Pim-2 and XIAP are over-expressed in prostate cancer cells.
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