垫状卷柏提取物诱导凋亡抗肿瘤作用研究（英文）  

Selaginella Pulvinata Extract Exerts Antitumor Efficacy in H22 Tumor-Bearing Mice via Induction of Apoptosis

作　　者：樊炼[1] 吴永平[2] 瞿慧[1] 吴信华 曹园[1] FAN Lian;WU Yong-ping;QU Hui;WU Xinhua;CAO Yuan(Affiliated Hospital of Nanjing University of Chinese Medicine,Jiangsu Province Hospital of Chinese Medicine,Nan jing,210029,China;Department of Medical Chemistry,Jiangsu Provincial Institute of Materia Medica,Nanjing,210009,China;School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,210023,China)

机构地区：[1]南京中医药大学附属医院/江苏省中医院,江苏南京210029 [2]江苏省药物研究所药化室,江苏南京210009 [3]南京中医药大学药学院,江苏南京210023

出　　处：《南京中医药大学学报》2019年第6期664-670,共7页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：国家自然科学基金(81102772);江苏省博士后基金(1302083B)

摘　　要：目的研究垫状卷柏提取物抗肿瘤作用及相关机制。方法采用皮下接种H22肝癌细胞株构建小鼠H22肝癌移植瘤模型,随机分为对照组(生理盐水)、5-FU组(30 mg/kg)、垫状卷柏提取物(SP)高、低剂量组(189、63 mg/kg),连续灌胃15 d。观察小鼠肿瘤生长情况,计算抑瘤率及肝、脾、胸腺指数;TUNEL法观察肿瘤组织细胞凋亡,Western blot测定凋亡相关蛋白的表达,qPCR检测Bax mRNA和Bcl-2 mRNA。结果与对照组比较,SP高、低剂量组小鼠体质量及肝、脾、胸腺指数均无显著差异;SP高、低剂量组小鼠的肿瘤质量均显著降低,呈现较高抑瘤率(P<0.01),且高剂量组与5-FU组相近;经TUNEL染色法观察,可见明显凋亡形态改变。qPCR检测表明,SP显著上调Bax mRNA的表达,下调Bcl-2 mRNA的表达。Western blot结果显示SP处理后,Bax、cytochrome c及cleaved caspase-3,caspase-8和caspase-9的表达显著上调(P<0.01),Bcl-2表达明显减弱,呈剂量依赖性。结论 SP有效抑制H22小鼠体内肿瘤生长,其机制与激活caspase诱导凋亡相关。OBJECTIVE To investigate the in vivo antitumor effect of S. pulvinata extract(SP) and its underlying mechanisms. METHODS A solid tumor H22-transplanted model in mice was established and randomly divided into normal saline control group, 5-FU chemotherapy group(30 mg/kg), low-dose SP group(63 mg/kg), and high-dose SP group(189 mg/kg). All mice received respective treatment once daily for 15 days. The tumor weights were monitored, and the inhibition rates as well as organ indexes were calculated. The potential mechanism was investigated using TUNEL staining, qPCR and Western blot analysis. RESULTS Compared with the control group, SP significantly inhibited tumor growth without producing obvious side-effects on body weight and immune organs. Observations from a TUNEL staining experiment demonstrated that SP noticeably induced apoptosis in tumor tissues. Moreover, qPCR showed that SP upregulated the mRNA levels of Bax and downregulated those of Bcl-2, resulting in the release of cytochrome c, which is in agreement with their protein expressions. Further Western blot analysis revealed that SP significantly activated and induced the cleavage of caspase-3, caspase-8 and caspase-9. CONCLUSION The findings clearly demonstrates that the mechanism of SP involves the induction of apoptosis. The study suggests that SP possesses potent in vivo antitumor effects against HCC.

关 键 词：垫状卷柏提取物 抗肿瘤 肝细胞癌 凋亡 

分 类 号：R285.5[医药卫生—中药学]