雷帕霉素对肝癌肝移植术后复发影响的实验研究  

Experimental Study on Effects of Recurrence after OLTx for HCC with Rapamine

作　　者：陈颖华[1] 蔡常洁[1] 陆敏强[1] 郭中敏[2] 陈规划[1] 

机构地区：[1]中山大学附属第三医院肝脏移植中心∥器官移植研究所,广东广州510080 [2]中山大学药学院实验动物中心,广东广州510080

出　　处：《中山大学学报（医学科学版）》2008年第3期248-251,263,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：科技部973计划项目(2003CB515507);广东省科技项目(2005B30501005);广东省自然科学基金(04105344);广州市科技计划项目(2005Z3-E0101)

摘　　要：【目的】探讨雷帕霉素对肝癌肝移植术后复发影响。【方法】应用MTT细胞增殖实验观察雷帕霉素对walker-256肿瘤细胞增殖的影响;应用流式细胞仪观察雷帕霉素对walker-256肿瘤细胞周期的影响;应用荧光定量RT-PCR观察雷帕霉素walker-256肿瘤细胞VEGFmRNA表达的影响。观察雷帕霉素对免疫抑制肝转移癌大鼠模型肿瘤生长情况、肿瘤组织PCNA指数、肿瘤复发率及生存情况的影响。【结果】MTT细胞增殖实验示雷帕霉素对walker-256肿瘤细胞有抑制作用,IC50为9.60ng/mL;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(P<0.05);雷帕霉素组VEGFmRNA表达为(4.50±0.13)×10-2较对照组[(70.8±1.3)×10-2]低(P<0.05)。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,两组间差别有统计学意义(P<0.05);雷帕霉素组荷瘤大鼠荷瘤肝质量比为(61.3±0.6)×10-3,较对照组[(70.8±1.3)×10-3]小,两组间差别有统计学意义(P<0.05);雷帕霉素组大鼠肿瘤复发率为90%,对照组为95%,两组比较差异无统计学意义;雷帕霉素组生存时间为(26.5±2.5)d,对照组为(14.8±2.3)d,两组间差别有统计学意义(P<0.05)。雷帕霉素组大鼠PCNA指数为64.1%±2.1%,较对照组(80.8%±1.0%)低,差别有统计学意义(P<0.05)。【结论】虽然雷帕霉素对降低免疫抑制下的肿瘤复发率作用不明显,但能明显抑制肿瘤生长速度,延长带瘤生存时间。[Objective] To study the effects of recurrence after orthotopic liver transplantation （OLTx） for hepato cellular carcinoma （HCC） with Rapamine. [Methods] MTr was used to detect the effects on the viability of the Walker-256 cells. Flow cytometry was used to detect the effects on the cell cycle of the Walker-256 cells. Realtime RT-PCR was used to detect the effects on the expression of vascular endothelial growth factor （VEGF） mRNA of the Walker-256 cells. The 40 wistar rats were chosen and randomly divided into 2 groups ： Rapamine group and control group. The walker-256 cell line was injected via portal venous in both groups. SRL group received the combined immunosuppression regime including Rapamine [MP＋ CSA＋ Rapamine]. Control group was applied the conventional combined immunosuppression regime （MP＋CSA）. During the experiment course of 60 days, weight of liver with tumor, hepatoweight-weight ratio, recrudescence rate and proliferating cell nuclear antigen （PCNA） labeling index of the tumor were recorded. [Results] MTr showed viability of walker-256 cells incubated with Rapamine was suppressed, and the IC50 was 9.60 ng/mL. Flow cytometry showed cell cycle of walker-256 cells 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 cells was lower in the Rapamin group （P 〈 0.05）. Weight of liver with tumor： Rapamine group （12.5 ± 0.2）g vs. control group （14.4 ± 0.3）g （P 〈 0.05）, hepatoweight-weight ratio： Rapamine group （61.3 ±0.6）× 10^-3, less than. control group （70.8± 1.3） ×10^-3（P 〈 0.05）. Recrudescence rate was 90% （18/20） in SRL group,vs. control group, 95% （19/20）, no significant difference （P 〉 0.05）. Survival time were （26.5± 2.5）d in Rapamine group, while longer than （14.8 ±2.3）d in control group （P 〈 0.05）. The PCNA labeling index was 64.1%± 2.1% in Rapamine group, and 80.8% ±1.0% in control group respectively. The difference

关 键 词：雷帕霉素 肝癌 肝移植 复发 

分 类 号：R363[医药卫生—病理学]