复方大七气汤联合顺铂对裸鼠卵巢癌皮下移植瘤Bcl-2/Bax表达的影响

Effects of compound Daqiqi decoction combined cisplatin on Bcl-2/Bax expression of nude mice ovarian cancer subcutaneous transplanted tumor

目的:探讨复方大七气汤(compound Daqiqi decoction,CDQD)联合顺铂对裸鼠卵巢癌皮下移植瘤细胞凋亡相关因子Bcl-2/Bax的影响,为临床治疗提供理论依据。方法:将成功建立裸鼠卵巢癌皮下移植瘤模型的40只荷瘤鼠随机分为5组(n=8):模型对照组、CDQD低、高剂量组、顺铂组、顺铂联合中药组,给药3周后处死所有荷瘤鼠剥离瘤体,测瘤体积、瘤重并绘制肿瘤生长曲线、计算抑瘤率,以RT-PCR法和Western blot法检测Bcl-2(B细胞白血病/淋巴瘤-2基因)、Bax(与Bcl-2相关的x蛋白)mRNA及蛋白量的表达。结果:①瘤重显示CDQD各剂量组瘤重均有一定程度减轻,与DDP组相比无统计学意义,顺铂联合中药组低于其余各组(P<0.01);肿瘤生长曲线显示与模型组比较,各用药组瘤体积均有不同程度缩小(P<0.01)。②RT-PCR结果显示促凋亡基因Bax mRNA的表达:与模型组比较,各用药组表达增高(P<0.01),其中顺铂联合中药组表达最高,与其余治疗组相比较差异有统计学意义(P<0.01);抑凋亡基因Bcl-2 mRNA在顺铂联合中药组表达最低(P<0.01),CDQD高剂量组与顺铂组比较差异无统计学意义。③Western blot法显示与模型组比较,各用药组表达增高(P<0.01),顺铂联合中药组中Bax蛋白的表达最高(P<0.01),CDQD高剂量组与顺铂组比较差异无统计学意义;Bcl-2蛋白在顺铂联合中药组表达最低(P<0.01);CDQD高剂量组与顺铂组比较差异无统计学意义。结论:CDQD对卵巢癌皮下移植瘤具有促凋亡作用,其机制可能与下调Bcl-2表达,上调Bax表达,促进肿瘤细胞凋亡有关;并且与顺铂联合用药具有增效作用。

Objective： To determine the compound Daqiqi decoction （CDQD） combined cisplatin plays on the cell apoptosis of sub- cutaneous transplanted ovarian cancer in node mice, to provide theory evidence for clinical treatment. Method： Making the models of subcutaneous transplanted ovarian cancer in nude mice, and divide the 40 mice with tumor into 5 groups （ n = 8 ）, the model control group, CDQD low dosed group, CDQD high dosed group, cisplatin group, cisplatin combined CDQD group, killing all the mice after 3 weeks＇ treatment and stripping tumors. Measure the volume and weight of the tumor and calculate tumor growth curve damps, the inhi- bition rate. Examining the expression of the Bcl-2（ B-cell leukemia/lymphoma 2） and Bax （ Bcl-2 associated x protein） mRNA and protein by the RT-PCR and the Western blot. Result： ①The tumor weight shows that there was certain lighter effect in each CDQD group, and compared with cisplatin groups has no statistical significance, the eisplatin combined CDQD group is obviously lighter than that of the other group（P 〈0. 01 ）. The tumor growth curve damps shows that compared with model control group, the treatment group tumors had some extent narrowing（P 〈 0. 01 ）. ②RT-PCR results： Bax （Bcl-2 associated x protein） mRNA expression shows that compared withmodel control group, the treatment group has increased（P 〈0. 01 ）, and the cisplatin combined CDQD group compared with the other group is the highest, there was significant difference with the rest of the treatment group （P 〈 0. 01 ）. In the Bcl-2 mRNA express lowest in cisplatin combined CDQD group （P 〈0. 01）, there has no difference between CDQD high dose group and cisplatin group. ③estem blot shows： com- pared with model control group, the Bax protein of treatment group has increased expression（ P 〈0. 01 ） ,the expression of Bax protein in cis- platin combined CDQD group is the highest（P 〈0. 01 ）. There has no difference between CDQD high dose group and cisplatin group. The Bcl-2 protein expression of the cisplatin combined CDQD group is the lowest（P 〈0. 01 ）, there has no difference between CDQD high dose group and cisplatin group. Conclusion： The effect of CDQD on stlbcutaneous transplantation ovarian tumor has promoting apoptosis function, its mechanism may be related to downgrade the Bcl-2 expression, higher expression of bax, stimulation on the apoptosis of tumor cells ; cispl- atin combined CDQD have synergistic effect.