MG132对卵巢上皮性癌裸鼠移植瘤生长的影响及联合顺铂作用效应的研究

MG132 Affects on the Nude Mice Transplanted Tumor Tissues of Ovarian Epithelial Carcinoma and the Relationship with Cispiatin Combination

目的:探讨蛋白酶体抑制剂MG132应用于卵巢上皮性癌裸鼠移植瘤的新型治疗及联合顺铂协同抗肿瘤的潜在价值和可行性。方法:建立人卵巢癌裸鼠皮下移植瘤模型,20只裸鼠随机平均分为4组,每日腹腔内注射给药1次,共7日。对照组(0.2 ml的0.9%氯化钠液),MG132组(2 mg/kg),顺铂组(1 mg/kg),联合组[MG132(2 mg/kg)+顺铂(1 mg/kg)]。移植瘤模型建立4周后比较各组移植瘤质量抑制率,IHC、FIA、Western blot、RT-PCR检测各组肿瘤促凋亡基因(Caspase3)、自噬基因(Beclin1)的表达情况。结果:1顺铂组、MG132组、联合组对移植瘤的瘤质量抑制率分别为15.38%、53.85%、88.46%,顺铂联合MG132理论相加的瘤质量抑制率为60.95%;2IHC、FIA、Western blot检测:与对照组相比,顺铂组、MG132组、联合组Beclin1、Caspase3阳性表达均明显增强,其中联合组阳性表达更强。3RT-PCR检测:顺铂组、MG132组、联合组的Beclin1、Caspase3 mRNA表达均明显高于对照组(P<0.05);且联合组又高于顺铂组、MG132组(P<0.05)。结论:MG132对卵巢上皮性癌裸鼠移植瘤生长具有抑制作用,且与顺铂联合治疗卵巢癌具有协同抗肿瘤效应,有望成为治疗顺铂耐药型难治性卵巢癌的一种有效抗肿瘤药物。

Objective：To investigate the potential value and feasibility of MG132 as a new therapy method for the ovarian cancer and a cisplatin chemotherapy-synergistic agent. Methods：The mode of the nude mice trans- planted tumor tissues of ovarian epithelial carcinoma were established,20 nude mice were randomly divided into four groups and were all intraperitoneal injected, once a day, a total of seven days：①Control group （0.2 ml saline） ,②MG132 group（2 mg/kg）,③Cisplatin group（1 mg/kg）,④Combination group[ MG132（2 mg/kg） ＋ cisplatin （1 mg/kg） ]. The weight inhibitory rates of tumors in each group were compared after four weeks. The expressions of Caspase3, Beclinl in each group were detected by I HC, FIA,western blot and RT-PCR. Results：①The in- hibitory rate of tumors in cisplatin group, MG132 group,and combination group was 53. 85% ,15. 38% ,88. 46%, respectively, the additive effect of cisplatin and MG132 combination therapy was 60. 95%. ②IHC, FIA, western blot detected that compared to control group, the positive expressions of Beclinl, Caspase3 were increased in cisplatin group,MG132 group,and combination group,among which combination group increased more. ③RT-PCR detected that the mRNA relative quantity of Beclinl in cisplatin group, MG132 group, combination group respectively were higher than that of control group（ P〈0. 05 ） ;and it was higher in combination group than that of cisplatin group and MG132 group（ P 〈0. 05 ）. Conclusions：The growth of nude mice transplanted tumor tissues of ovarian epithelial carcinoma can be inhibited by MG132,and has a synergistic effect for treating ovarian cancer by combination with cisplatin,it is expected to be an effective anti-tumor drug for platinum resistant refractory ovarian cancer.