PKC412联合阿霉素对大鼠膀胱肿瘤生长及细胞凋亡的影响

Effects of PKC412 combined with adriamycin on growth and apoptosis of bladder cancer cells in rats

目的探讨蛋白激酶C(PKC)抑制剂PKC412对大鼠膀胱肿瘤的生长和细胞凋亡的影响。方法培养大鼠膀胱癌T739细胞,建立T739大鼠原位膀胱癌模型1周后分为模型对照(A组)、阿霉素膀胱灌注治疗(B组)、阿霉素联合PKC412 1μmol/L膀胱灌注治疗(C组)和阿霉素联合PKC412 10μmol/L膀胱灌注治疗(D组)。8周后处死大鼠,观察肿瘤大小,测定CD31表达,计算微血管密度(MVD),TUNEL法测定肿瘤细胞凋亡。结果 8周后,B、C、D组的膀胱肿瘤的重量均小于A组,D组大于B、C组(P<0.01)。D组MVD低于B、C组(P<0.01)。A、B、C和D组肿瘤细胞凋亡指数分别为5.74±1.36、11.53±1.68、13.44±1.96和21.64±1.58,D组肿瘤细胞凋亡率高于B、C组(P<0.01)。结论阿霉素联合PKC412对膀胱癌细胞生长和增殖抑制作用大于单用阿霉素。

Objective To investigate the effects of protein kinase C（PKC）inhibitor PKC412combined with adriamycin（ADM）on the growth and apoptosis of bladder cancer cells in rats.Methods The bladder cancer cell line T739was cultured.The orthotopic bladder cancer model was established in 40rats,which were equally divided into four groups of A（model control）,B（treated with ADM）,C（treated with ADM and PKC412 1μmol/L）and D（treated with ADM and PKC412 10μmol/L）.The drugs were given by bladder perfusion started 1week after the model was established.After 8weeks,the rats were killed for observing tumor weight,detecting CD31expression for calculating microvessel density（MVD）and determining tumor cell necrosis by TUNEL method.Results The tumor weight was higher in groups of B,C and D than that in group A（P〈0.01）,which was higher in group D than that in groups of B and C（P〈0.01）.The MVD was lower in group D than that in groups of B and C（P〈0.01）.The apoptosis indexes of the tumor cells in groups of A,B,C and D were 5.74±1.36,11.53±1.68,13.44±1.96and 21.64±1.58,respectively,which were higher in group D than those in groups of B and C（P〈0.01）.Conclusion The suppressive effect of PKC412combined with ADM on the growth and proliferation is more than that of ADM in rats with bladder cancer.