雷帕霉素对大鼠肝癌的抑制作用及其机制  

Mechanism and significance of suppression on tumor recurrence after liver transplantation with rapamine

作　　者：蔡常洁[1] 陈颖华[1] 陆敏强[1] 陈规划[1] 

机构地区：[1]中山大学附属第三医院肝移植中心中山大学器官移植研究所,广州510630

出　　处：《中华实验外科杂志》2008年第7期834-836,共3页Chinese Journal of Experimental Surgery

基　　金：广东省科技计划资助项目（2005B30501005）;广东省自然科学基金资助项目（04105344）

摘　　要：目的探讨雷帕霉素对大鼠肝癌抑制作用及其机制。方法40只大鼠随机等分为雷帕霉素组、对照组，观察雷帕霉素对大鼠经门静脉播散的肝脏复发肿瘤复发率和生存情况影响。应用噻唑蓝（MTT）比色法观察其对walker-256肿瘤细胞增殖影响；应用流式细胞仪观察其对肿瘤细胞周期影响；应用荧光定量聚合酶链反应（PCR）观察其对肿瘤细胞血管内皮生长因子（VEGF）mRNA表达影响。结果雷帕霉素组荷瘤大鼠荷瘤肝重为（12.5±0.2）g，较对照组（14．4±0．3）g轻，两者差异有统计学意义（P〈0．05）；雷帕霉素组荷瘤大鼠荷瘤肝重比为（61．3±0.6）×10^-3，较对照组（70．8±1．3）×10^-3小，两者差异有统计学意义（P〈0.05）；雷帕霉素组大鼠肿瘤复发率为90％，对照组为95％，两者差异无统计学意义（P〉0．05）；雷帕霉素组生存时间为（26.5±2．5）d，对照组为（14．8±2．3）d，两者差异有统计学意义（P〈0．05）。MTT比色法示雷帕霉素对walker-256肿瘤细胞有抑制作用，IC50为9．60μg／L；细胞周期检测示雷帕霉素组G1／G0期比例为（55.2±0.1）％，较对照组（45．2±0．4）高，两者差异有统计学意义（P〈0.05）；雷帕霉素组VEGFmRNA表达（4．50±0.13）×10^-2较对照组（70.8±1．3）×10^-2低，两者差异有统计学意义（P〈0．05）。结论雷帕霉素通过抑制肿瘤细胞倍增和减少促肿瘤血管内皮生长因子的表达来延长宿主荷瘤生存时间。Objective To study the mechanism and significance of suppression on tumor recurrence after liver transplantation with Rapamine. Methods 40 rats were divided equally into 2groups, Rapa group and control group. The recurence data of the HCC recurence after OLTx. model were observed. The MTT assays were tested to detect the affects of Rapamine to the viability of tumor cell line. The ceil cycle tests were checked by FACS. And real-time RT-PCR was used to detect the effects on the expression of VEGF mRNA of the walker-256 cells. Results Weight of liver with tumor ： RAPA group （ 12.5 ± 0.2） g, vs. control group（ 14.4 ± 0.3 ） g （ P 〈 0.05 ） , hepatoweight-weight ratio ： RAPA group （ 61.3 ± 0.6 ） x 10-3 , less than. control group （70.8 ± 1.3 ） x 10-3 （ P 〈 0.05 ）. Recrudescence rate was 90% （ 18/20 ） in RAPA group ,vs. control group ,95% （ 19/20 ） , no significant difference （ P 〉 0.05 ）. Survival time were （26.5 ±2.5） d in RAPA group,while longer than （14.8 ±2.3） d in control group （P 〈0.05）. MTT showed viability of walker-256 ceils incubated with Rapamine was suppressed, and the IC50 was 9.60 μg/L. Flow cytometry showed cell cycle of walker-256 ceils in Rapamine group was arrested in stage of G1/G0 （ P 〈 0.05 ）. Real-time RT-PCR showed the expression of VEGF mRNA in walker-256 ceils was lower in the Rapamin group （ P 〈 0.05 ）. Conclusion Rapamine can prolong the survival time by suppressing the viabilities of tumor ceils and down-regulating expression of VEGF mRNA.

关 键 词：雷帕霉素 癌 肝细胞 复发 

分 类 号：R735.7[医药卫生—肿瘤]