芹菜素对裸鼠肝癌皮下移植瘤抑制作用研究.docVIP

芹菜素对裸鼠肝癌皮下移植瘤抑制作用研究 　　[摘要] 目的 探?芹菜素（APG）对裸鼠肝癌皮下移植瘤的抑制作用及其相关机制。 方法 建立人肝癌阿霉素（ADM）耐药细胞BEL-7402/ADM裸鼠皮下移植瘤模型，24只移植成功的裸鼠随机分为三组：对照组（ADM 3 mg/kg）、APG组（APG 50 mg/kg+ADM 3 mg/kg）和miR-101 mimics组（miR-101 mimics 5 mg/kg+ADM 3 mg/kg），每组8只。上述药物每3天注射l次，共7次。给药结束后处死裸鼠，切取移植瘤组织。免疫组化法检测Ki-67蛋白表达评价肿瘤细胞增殖，免疫蛋白印迹法检测肿瘤组织核转录因子红细胞系相关因子-2（Nrf2）蛋白的表达，qRT-PCR法测定移植瘤组织miR-101水平。 结果 与对照组相比，APG和miR-101 mimics能显著抑制肿瘤生长（P 0.05），抑制肿瘤细胞增殖（P 0.05或P 0.01），此外，APG和miR-101 mimics还能下调肿瘤组织Nrf2蛋白的表达（P 0.01），上调miR-101表达（P 0.05）。 结论 APG能有效抑制肝癌移植瘤生长，其机制可能与抑制肿瘤细胞增殖，上调miR-101表达和下调Nrf2表达有关。 　　[关键词] 芹菜素；肝癌；化疗增敏；核转录因子红细胞系相关因子-2；miR-101 　　[中图分类号] R965 [文献标识码] A [文章编号] 1673-7210（2017）09（b）-0009-04 　　Inhibiting effect of apigenin on hepatocellar carcinoma xenografts in nude mice 　　GAO Aimei1 CHENG Xiaoli2 　　1.Department of Pharmacy， the Fifth People′s Hospital of Shanghai， Fudan University， Shanghai 200240， China； 2.Department of Pharmacy， Shenzhen Bao′an District Maternity and Child Health Care Hospital， Guangdong Province， Shenzhen 518133， China 　　[Abstract] Objective To investigate the effect of apigenin （APG） on hepatocellar carcinoma xenografts in nude mice and the possible molecular mechanism. Methods Models of nude mice were transplanted with BEL-7402/doxorubicin （ADM）， and randomly divided into 3 groups， each group had 8 mice. The groups of mice were treated i.p. as follow： ADM （3 mg/kg， control group）， APG+ADM （50 mg/kg+3 mg/kg， APG group）， miR-101 mimics +ADM （5 mg/kg+3 mg/kg， miR-101 mimics group）， every three days for a total of seven times. The volumes of tumor were measured. After the end of medication， the mice were sacrificed for measurement of tumor weights. Tumor cell proliferation was analyzed by Ki-67 immunostaining. Nuclear factor erythroid-2-related factor 2 （Nrf2） protein level was measured by Western blot. miR-101 level was detected by Real-time PCR. Results The volumes and weights of tumors in APG group and miR-101 mimics group were decreased compared with the control group （P 0.05