YAP抑制药Verteporfin增强肝细胞癌导管动脉化疗栓塞术治疗大鼠的疗效  

The YAP inhibitor Verteporfin enhances the efficacy of catheterized arterial chemoembolization for hepatocellular carcinoma in rats

作　　者：高兴强 窦晓静 郭燕春 王其亮 GAO Xing-qiang;DOU Xiao-jing;GUO Yan-chun;WANG Qi-liang(Interventional Medicine Department,Qingdao Traditional Chinese Medicine Hospital(Qingdao Hiser Hospital),Qingdao Hiser Hospital Affiliated of Qingdao University,Qingdao 266033,Shandong Province,China;Pharmacy Department,Qingdao Traditional Chinese Medicine Hospital(Qingdao Hiser Hospital),Qingdao Hiser Hospital Affiliated of Qingdao University,Qingdao 266033,Shandong Province,China;Oncology Department,Qingdao Traditional Chinese Medicine Hospital(Qingdao Hiser Hospital),Qingdao Hiser Hospital Affiliated of Qingdao University,Qingdao 266033,Shandong Province,China)

机构地区：[1]青岛市中医医院(市海慈医院)、青岛大学附属青岛市海慈医院介入医学科,山东青岛266033 [2]青岛市中医医院(市海慈医院)、青岛大学附属青岛市海慈医院药剂科,山东青岛266033 [3]青岛市中医医院(市海慈医院)、青岛大学附属青岛市海慈医院肿瘤科,山东青岛266033

出　　处：《中国临床药理学杂志》2023年第20期2970-2974,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的 观察Yes相关蛋白抑制药Verteporfin联合经导管动脉化疗栓塞术(TACE)治疗对N-亚硝基二乙胺(DEN)诱导肝癌大鼠肿瘤生长的抑制作用。方法 用DEN饲喂法构建肝癌大鼠,并将建模成功的大鼠随机分为对照组、TACE组(给予TACE治疗)、Verteporfin组(腹腔注射10 mg·kg^(-1) Verteporfin)和联合组(TACE治疗+腹腔注射10 mg·kg^(-1) Verteporfin),每组17只大鼠,连续治疗7 d。观察各组大鼠生存时间并测量肿瘤体积;以TUNEL法检测各组大鼠肿瘤组织细胞凋亡情况;以蛋白质印迹(Western blot)法检测各组大鼠肿瘤组织相关蛋白表达水平;以免疫组化检测CD34表达评估微血管密度(MVD)。结果 对照组、TACE组、Verteporfin组、联合组大鼠生存时间分别为(13.57±1.40)、(16.14±2.03)、(16.43±1.84)、(26.71±1.16) d,肿瘤增长倍数分别为12.61±2.04、9.75±1.17、9.58±1.17、4.82±0.57,TUNEL阳性细胞率分别为(2.64±0.54)%、(9.96±0.88)%、(10.08±0.93)%、(20.20±0.89)%;MVD水平分别为41.00±4.52、39.44±4.47、34.89±2.73、17.89±1.66,缺氧诱导因子1α(HIF-1α)蛋白水平分别为1.06±0.11、0.78±0.08、0.72±0.08、0.35±0.07,血管内皮生长因子(VEGF)蛋白表达水平分别为0.84±0.08、0.67±0.04、0.66±0.08、0.28±0.06。与对照组比较,TACE组、Verteporfin组、联合组的上述指标差异均有统计学意义(均P<0.05);联合组的上述指标分别与TACE组、Verteporfin组比较,差异均有统计学意义(均P<0.05)。结论 TACE联合Verteporfin治疗较TACE或Verteporfin可进一步抑制肝癌肿瘤生长及肿瘤微血管生成,并诱导肿瘤细胞凋亡,发挥抗肿瘤作用。Objective To observe the inhibitory effect of Yes-associated protein inhibitor Verteporfin combined with transcatheter arterial chemoembolization (TACE) on diethylnitrosamine (DEN) induced tumor growth in rats with hepatocellular carcinoma.MethodsHepatocellular carcinoma rats were constructed by DEN feeding method,and the rats were randomly divided into control group,TACE group(TACE treatment),Verteporfin group (intraperitoneally injected 10mg·kg^(-1)verteporfin) and TACE+Verteporfin group (TACE treatment+intraperitoneally injected 10 mg·kg^(-1)Verteporfin),with 17 rats in each group.The treatment lasted for 7 days.The survival time of each group were observed and the tumor volume were measured.TUNEL method was used to detect the apoptosis of tumor cells in each group.The expression levels of related proteins in tumor tissues of each group were detected by Western blot.Immunohistochemical detection of CD34 expression to evaluate microvessel density (MVD).Results The survival time of rats in control group,TACE group,Verteporfin group and TACE+Verteporfin group were (13.57±1.40),(16.14±2.03),(16.43±1.84),(26.71±1.16) d,respectively;tumor growth times were 12.61±2.04,9.75±1.17,9.58±1.17,4.82±0.57,respectively;TUNEL positive cells rate were (2.64±0.54)%,(9.96±0.88)%,(10.08±0.93)%,(20.20±0.89)%,respectively;the MVD levels were 41.00±4.52,39.44±4.47,34.89±2.73,17.89±1.66,respectively;HIF-1α protein levels were 1.06±0.11,0.78±0.08,0.72±0.08,0.35±0.07,respectively;the expression levels of VEGF protein were 0.84±0.08,0.67±0.04,0.66±0.08,0.28±0.06,respectively.Compared with the control group,the above indexes of TACE group,Verteporfin group and TACE+Verteporfin group were significantly different (all P0.05).Compared with TACE group,Verteporfin group,the above indexes in TACE+Verteporfin group were significantly different (all P0.05).Conclusion Compared with TACE or verteporfin therapy,TACE combined with Verteporfin therapy further inhibits tumor growth and tumor angiogenesis,induces tumor cell ap

关 键 词：VERTEPORFIN 肝癌 肿瘤生长 经导管肝动脉化疗栓塞术 血管生成 

分 类 号：R979.1[医药卫生—药品]