摘要
目的探讨PI3Kγ抑制剂AS605240抗小鼠乳腺癌的效果与相关机制。方法选择BALC小鼠30只,通过皮下注射4T1小鼠乳腺癌细胞株建立乳腺癌小鼠模型,肿瘤形成后30只BALC小鼠分为对照组、空载组与AS605240组各10只,对照组口服与AS605240组等体积DMSO;空载组口服Ad-vector、DMSO溶液各10μL;AS605240组口服AS605240溶液10μL,观察、记录肿瘤组织变化情况并进行蛋白杂交分析。结果治疗后各组BALC小鼠均未死亡,AS605240组肿瘤体积为(378.41±56.11)mm3,小于空载组(2 533.42±123.33)mm3和对照组(2 440.42±186.48)mm3,差异有统计学意义(P <0.05)。治疗后AS605240组的细胞凋亡指数为(22.81±3.12)%,高于空载组与对照组的(3.79±1.33)%和(3.29±1.92)%,差异有统计学意义(P<0.05)。蛋白质印迹检测显示,与空载组、对照组对比,治疗后AS605240组肿瘤组织标本的PCNA、CyclinD1、Caspase-3蛋白表达量降低,差异有统计学意义(P<0.05)。结论 PI3Kγ抑制剂AS605240在体内具有一定的抑制小鼠乳腺癌增殖的作用,可促使肿瘤组织细胞凋亡,其作用机制可能与调节PCNA、CyclinD1、Caspase-3表达有关。
Objective To study the anti-breast cancer effect of the PI3Kγ inhibitor AS605240 in mice and its mechanism. Methods A total of 30 BALB mice were selected and used to construct the model mice with breast cancer by subcutaneous injection of 4T1 mice breast cancer cell strains. After the tumor formation, those mice were divided the control group, and AS605240 group with 10 mice in each group. The control group was administered orally with 10 o DMSO solution, the empty vector group was treated orally with 10μL Ad-vector solution and 10μL DMSO solution, and the AS605240 group was given orally 10μL AS605240 solution. The changes of tumor tissues were observed and recorded and the protein blot analysis was carried out. Results There were no dead mice in each group after treatment. The tumor volume were of the AS605240 group was (378.41±56.11)mm3 and it was significantly less than the tumor volumes of the empty vector group and the control group which were (2533.42±123.33)mm^3 and (2440.42±186.48)mm^3 ( P <0.05) respectively. The apoptosis index of the AS605240 group was (22.81 +3.12)% and it was significantly higher than the apoptosis indexes of the empty vector group and the control group which were (3.79 +1.33)% and (3.29 +1.92)% respectively ( P <0.05). The results of western blot analysis showed that the protein expression levels of PCNA, CyclinD1 and Caspase-3 in the AS605240 group were significantly lower than those in the empty vector group and the control group after treatment ( P <0.05). Conclusion The PI3Kγ inhibitor AS605240 has a certain inhibitory effect in vivo on the proliferation of breast cancer in mice by promoting the apoptosis of tumor cells and its mechanism may be related with the expression regulation of PCNA, CyclinD1and Caspase-3.
作者
金科
朱剑梅
赵丹
Jin Ke;Zhu Jianmei;Zhao Dan(Department of Oncology,East Department of Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital,Chengdu 610000,China)
出处
《成都医学院学报》
CAS
2019年第2期149-152,共4页
Journal of Chengdu Medical College
基金
四川省卫生和计划生育委员会科研课题(No:140082)
