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目的探讨8-氯-环磷酸腺苷(8-Cl-cAMP)及其代谢物8-氯-腺苷(8-Cl-adenosine)靶向蛋白激酶A RⅠα(PKA RⅠα)抑制PC3M肿瘤生长的作用。方法采用MTT法检测PC3M细胞增殖;TUNEL法检测细胞凋亡;Western blot检测RⅠα、RⅡβ、Caspase-3、Bcl-2、p38丝裂原活化蛋白激酶(MAPK)和磷酸化p38 MAPK表达。结果 8-Cl-cAMP和8-Cl-adenosine抑制PC3M细胞生长(P<0.05),引起细胞凋亡(P<0.05),下调RⅠα表达,上调RⅡβ表达,激活磷酸化p38 MAPK,抑制Caspase-3和Bcl-2表达。结论 8-Cl-cAMP及其代谢物8-Cl-adenosine靶向PKA RIα抑制PC3M肿瘤生长。其机制可能通过cAMP/PKA通路激活MAPK通路起作用。
Objective To investigate the inhibitory effect of 8-Cl-cAMP and its metabolite 8-Cl-adenosine on the growth of PC3M cells induced by PKA RⅠα . Methods The proliferation of PC3M cells was detected by MTT assay. The apoptosis of PC3M cells was detected by TUNEL method. The expressions of RⅠα, RⅡβ, Caspase-3, Bcl-2, p38 mitogen-activated protein kinase (MAPK) and phospho-p38 MAPK were detected by Western blot. Results 8-Cl-cAMP and 8-Cl-adenosine could inhibit the growth of PC3M cells (P <0.05) and induce apoptosis (P <0.05), downregulate the expression of RⅠα, upregulate the expression of RⅡβ, activate the phosphorylation of p38 MAPK and inhibit the expression of Caspase-3 And Bcl-2 expression. Conclusions 8-Cl-cAMP and its metabolite 8-Cl-adenosine target PKA RIα to inhibit PC3M tumor growth. Its mechanism may activate MAPK pathway through cAMP / PKA pathway.