丹参酮ⅡA对膀胱癌裸鼠移植瘤增殖的影响及相关机制

Effect of TanshinoneⅡA on proliferation of bladder carcinoma in nude mice and its mechanishm

目的探讨丹参酮ⅡA(TanⅡA)对膀胱癌细胞体内增殖的影响以及相关机制。方法将膀胱癌T24细胞注射到20只裸鼠皮下,建立裸鼠膀胱癌动物模型。1周后,随机分为对照组(n=10)和TanⅡA组(n=10),分别腹腔内注射生理盐水和TanⅡA(15mg/kg,1次/3d),并且开始定期测量瘤体大小(1次/3d),连续6次,绘制肿瘤增殖曲线。末次给药24h后,处死小鼠,RTPCR检测两组裸鼠肿瘤组织中Aurora A、HIF-1α和Bcl-2 mRNA表达水平。结果相比对照组,TanⅡA能够明显抑制T24细胞在裸鼠皮下的增殖,呈时间依赖性,并且可以显著降低TanⅡA组肿瘤组织中Aurora A(P<0.000 1)、HIF-1α(P=0.004 7)和Bcl-2(P=0.000 5)mRNA表达水平。结论 TanⅡA可能通过降低Aurora A、HIF-1α和Bcl-2的表达水平,抑制膀胱癌的增殖,发挥抗膀胱癌的作用。

Objective To explore the effect of TanshinoneⅡA(TanⅡA)on the proliferation of bladder carcinoma and the expression of Aurora A,HIF-1αand Bcl-2 in vivo.Methods Bladder cancer T24 cells were implanted subcutaneously into nude mice which were randomly into two groups to be treated with vehicle,TanⅡA(15 mg/kg of body weight,Q3d)and normal saline.Each agent was injected intraperitoneally,with treatment starting 7 days after inoculation with T24 cells.Tumor size was measured at regular interval(Q3d)until 25 days after inoculation and the tumor proliferation curves of two groups were drawn.The messenger RNA expression of Aurora A,HIF-1αand Bcl-2 in T24 xenograft tumors tissues were detected by Real-time PCR.Results Treatment with TanⅡA resulted in a marked reduction in tumor size and down-regulated significantly the messenger RNA expression of Aurora A(P<0.000 1),HIF-1α(P=0.004 7)and Bcl-2(P=0.000 5)in the T24 xenograft tumors compared with the control group.Conclusions The potential anti-tumor effect of TanⅡA was attested by inhibition of proliferation of bladder carcinoma through reduction in the expression of Aurora A,HIF-1αand Bcl-2 in vivo.