The roles of protein kinase C and cyclic adenosine monophosphate signal transduction in apoptosis of bladder cancer induced by arsenic trioxide / 中华泌尿外科杂志

ABSTRACT

Objective To investigate if apoptosis induced by arsenic trioxide(As_2O_3)on bladder cancer T24 cell line is related to the alteration of protein kinase C and cyclic adenosine monophosphate (PKC-cAMP)and its possible mechanism.Methods Apoptosis was studied by TUNEL method.Radio- immunoassay and enzyme immunoassay methods were used to detect the PKC-cAMP alteration in apoptotic process.The expressions and activation of caspase3 were observed by immunocytochemical method and Western blot.Results Atter 24-h drug treatment,the cell apoptosis induced by different concentrations of As_2O_3 was detected by TUNEL method.In control group,the apoptosis rate was 0.86%;PKC level was 2.55 pmol?min~(-1)??g~(-1);cAMP concentration was 22.56 pmol/ml;the expression rate of caspase3 was 8.01%.Compared with control group,the apoptosis rates of 5?mol/L and 10?mol/L As_2O_3 groups increased 8.51-fold and 13.33-fold,respectively;PKC Level decreased 59.22% and 64.71%,respectively;cAMP in- creased 5.34-fold and 4.23-fold,respectively;expression rates of caspase3 increased 3.96-fold and 6.76- fold,respectively.The differences were significant(P＜0.05).Compared with As_2O_3 groups,apoptosis rates of 5?mol/L and 10?mol/L As_2O_3+100nmol/L phorbol 12-myristate 13-aectate(PMA)groups decreased 40.22% and 45.58%,respectively;PKC increased 1.00-fold and 0.76-told,respectively;cAMP decreased 8.37% and 31.46%,respectively;expression rates of caspase3 decreased 51.09% and 65.03%,respective- ly.Activation of caspase3 was detected in As_2O_3-treated groups and As_2O_3+100 nmol/L PMA-treated groups;and activations of caspase3 in PMA-treated groups were weaker than those in As_2O_3-treated groups. Conclusions The antitumor mechanism of As_2O_3 may be the induction of bladder cancer T24 cell apopto- sis by decreasing PKC and increasing cAMP level.