右美托咪定对人前列腺癌PC3细胞增殖、侵袭及成瘤能力的影响及机制研究

Effects of dexmedetomidine on the proliferation,invasiveness and tumorigenesis of human prostate cancer PC3 cells and its action mechanism

目的:分析右美托咪(Dex)对人前列腺癌PC3细胞增殖、侵袭及成瘤能力的影响与机制。方法:人前列腺癌PC3细胞分为对照组、Dex 1组、Dex 2组、Dex 3组,分别采用0、1、2、5μmol/L Dex处理。CCK8法检测各组细胞增殖能力,流式细胞仪检测各组细胞凋亡情况,Transwell检测各组细胞侵袭能力,裸鼠移植瘤检测成瘤能力,Western印迹检测各组细胞丝裂原活化蛋白激酶(MAPK)信号通路相关蛋白的表达。结果:对照组、Dex 1组、Dex 2组、Dex 3组PC3细胞A值随时间延长而升高(P<0.05),与对照组比较,Dex 1组、Dex 2组、Dex 3组PC3细胞A值随Dex剂量的增加而降低,凋亡率随Dex剂量的增加而升高(P<0.05);与对照组比较,Dex 1组、Dex 2组、Dex 3组细胞凋亡率与细胞穿膜数量随Dex剂量的升高而降低(P<0.05);对照组、Dex 1组、Dex 2组、Dex 3组裸鼠移植瘤体积随时间延长而增大(P<0.05),与对照组比较,Dex 1组、Dex 2组、Dex 3组移植瘤体积随Dex剂量的增加而缩小(P<0.05)。与对照组比较,Dex 1组、Dex 2组、Dex 3组磷酸化细胞外信号调节激酶(p-ERK)/细胞外信号调节激酶(ERK)、磷酸化c-Jun氨基末端激酶(p-JNK)/c-Jun氨基末端激酶(JNK)随剂量增加而降低(P<0.05)。结论:Dex能抑制人前列腺癌PC3细胞增殖、侵袭,促进凋亡,降低其成瘤能力,其机制与MAPK信号通路中ERK、JNK磷酸化活性下降有关。

Objective:To investigate the effects of dexmedetomidine(Dex)on the proliferation,invasiveness and tumorigenesis of human PCa PC3 cells and its action mechanism.Methods:We treated human PCa PC3 cells with Dex at 0μmol/L(the control group),1μmol/L(Dex group 1),2μmol/L(Dex group 2),and 5μmol/L(Dex group 3).After 24,48 and 72 hours of treatment,we examined the proliferation,apoptosis and invasiveness of the cells using cell counting kit-8(CCK8),flow cytometry and Transwell assay respectively,measured the tumorigenicity of the transplanted tumors in the nude mice,and determined the expressions of mitogen-activated protein kinase(MAPK)signaling pathway-related proteins in the cells by Western blot.Results:After treatment,the A value of the PC3 cells was significantly increased in all the four groups(P<0.05).Compared with the control group,the three Dex groups showed a decrease in the A value,an elevated rate of apoptotic cells(P<0.05),an increased number of membrane-penetrating cells(P<0.05),reduced volume of the transplanted tumors(P<0.05),and down-regulated expressions of phosphorylated extracellular signal-regulated kinase(p-ERK)/ERK and phosphorylated c-Jun N-terminal kinase(p-JNK)/JNK(P<0.05)with the increased dose of Dex.The volume of the transplanted tumors in the nude mice was increased in all the four groups in a time-dependent manner(P<0.05).Conclusion:Dex inhibits the proliferation and invasiveness,promotes the apoptosis,and reduces the tumorigenicity of human PCa PC3 cells by decreasing the phosphorylation of ERK and JNK in the MAPK signaling pathway.