中文摘要：

目的研究相思子蛋白P2对肝癌细胞生长的抑制作用及机制。方法体外实验：MTT法检测相思子蛋白P2对人肝癌HepG2细胞增殖的抑制作用。流式细胞仪检测对HepG2细胞周期和细胞凋亡的影响。TRAP-SYBR—Green染色法检测相思子蛋白P2作用前后细胞端粒酶活性的改变。体内实验：相思子蛋白P250、75、100ug·kg-1。连续灌胃给药10d，观察对小鼠肝癌H22移植性肿瘤的生长抑制作用。小鼠口服给药急性毒性观察。结果相思子蛋白P2可明显抑制HepG2细胞增殖，IC50值为5．172×10^-3mg·L^-1。在5×10^-5～1×10^-5mg·L^-1剂量作用下，可引起HepG2细胞凋亡。相思子蛋白P2主要将细胞周期滞留在S期，从而抑制了肿瘤细胞增殖。同时可使细胞端粒酶活性明显降低，其下调端粒酶活性的作用随药物浓度的增加而明显增强。相思子蛋白P2对小鼠H22肝癌细胞生长有明显抑制作用，100ug·kg-1抑瘤率达62．47％，且对胸腺和脾脏指数的影响较环磷酰胺小。小鼠口服给药LD50值为6．77mg·kg-1。结论相思子蛋白P2体内外均可明显抑制肝癌细胞的生长，其抗肿瘤作用可能与下调细胞端粒酶活性、改变细胞周期分布，诱导细胞凋亡有关。

英文摘要：

Aim To investigate the effects of Abrin P2 on the inhibition of the proliferation of liver cancer cells,and to explore its mechanism.Methods In vitro：the effects of Abrin P2 on HepG2 cell proliferation were evaluated by MTT assay.Flow cytometry analysis was applied to detect apoptosis and cell cycle distribution.The change of the telomerase activation was examined by TRAP-SYBR-Green staining method.In vivo：intragastrically administered Abrin P2（50,75,100 μg·kg-1） to mice for successive 10 days,H22 tumors xenografted in mice were used to evaluate the anti-tumor effects of Abrin P2.Acute toxicity of Abrin P2 orally administrated to mice was observed.Results Cell proliferation was inhibited in HepG2 cells treated with Abrin P2,and the value of IC50 was 5.172×10-3 mg·L-1 after 48 h.Abrin P2 significantly induced HepG2 cell apoptosis in 5×10-5~1×10-3 mg·L-1.Abrin P2 arrested the cell cycle at S phase and inhibited the cell proliferation.Subsequently,the telomerase activation was decreased obviously in a dose-dependent manner.In addition,the anti-tumor effects of Abrin P2 were further confirmed by inhibition growth of H22 tumors xenografted in mice,with a tumor inhibitory rate of 62.47% at the dose of 100 μg·kg-1.And the effects on thymus index and spleen index were lower compared to the cyclophosphamide group.The value of LD50 of mice orally administrated was 6.77 mg·kg-1.Conclusions Abrin P2 can inhibit the proliferation of hepatoma in both vitro and vivo,and the effects may be related with the down-regulation of telomerase activation,the change of cell cycle distribution（S phase arrest） and the induction of cell apoptosis.