中文摘要：

目的观察叶下珠复方Ⅱ号对肝癌HepG2细胞裸鼠移植瘤生长的抑制作用,并探讨其作用机制。方法建立BALB/C裸鼠肝癌HepG2细胞皮下移植瘤模型,随机分为模型组,叶下珠复方Ⅱ号高、中、低剂量组（17.28,8.64,4.32 g·kg^-1）和氟尿嘧啶（5-Fu）组（0.025 g·kg^-1）,给药6周后处死裸鼠,剥离瘤组织称质量。体外观察叶下株复方Ⅱ号对HepG2细胞增殖、集落形成、细胞周期和细胞凋亡的影响,观察药物作用后Wnt1和β-catenin基因mRNA表达的改变。结果叶下珠复方Ⅱ高、中、低剂量组对裸鼠HepG2肝癌细胞移植瘤生长的抑制作用明显,与模型组比较,肿瘤质量均明显减轻（P〈0.01）,但与5-Fu组比较,差异均无统计学意义（P〉0.05）。叶下珠复方Ⅱ号体外在10 mg·mL^-1以上浓度能明显抑制肝癌Hep G2细胞的增殖,呈明显的量-效关系和时-效关系;叶下珠复方Ⅱ号在2 mg·mL^-1以上浓度,对HepG2细胞集落形成呈明显的抑制作用;叶下珠复方Ⅱ号以15,20 mg·mL^-1浓度作用HepG2细胞48 h后,G0/G1期细胞比例明显降低,S期细胞比例显著增加,与细胞对照组比较,差异均具有统计学意义（P〈0.01）;叶下珠复方Ⅱ号在10,15,20 mg·mL^-1浓度,作用于HepG2细胞48 h,细胞早期凋亡率和总凋亡率明显增加,与细胞对照组比较,差异均具有统计学意义（P〈0.01）。叶下珠复方Ⅱ号高、低剂量组（20,10 mg·mL^-1）作用于HepG2细胞48 h后,Wnt1和β-catenin基因m RNA的表达量均明显低于细胞对照组（P〈0.01,P〈0.05）。结论叶下珠复方Ⅱ号对BALB/C裸鼠肝癌HepG2细胞皮下移植瘤的生长具有明显的抑制作用,作用机制与抑制Wnt1/β-catenin基因表达和信号通路活化,从而阻滞细胞周期、抑制细胞增殖和诱导细胞凋亡有关。

英文摘要：

Objective To observe the inhibitory effect of Compound Phyllanthus Urinsria Ⅱ（CPUⅡ）on the growth of HepG2 cells xenograft tumor in BALB/C nude mice,and to investigate the anti-liver cancer mechanism.Methods After the establishment of xenograft tumor BALB/C mouse model induced by subcutaneous injection with HepG2 cells,all the model mice were randomly divided into five groups,model group,5-fluracil（Fu）control group（0.025 g·kg^-1,and high-,medium-and low-dose CPUⅡgroups（in the dose of 17.28,8.64,4.32 g·kg^-1,respectively）.After treatment for 6 consecutive weeks,mice were sacrificed for the extraction of tumor mass.Effects of CPUⅡon cell proliferation,colony formation,cell cycle,apoptosis of HepG2 cells in vitro were observed,and the mR NA expression levels of Wnt1 and β-catenin were measured.Results Tumor weight in the three CPUⅡ groups were all significantly reduced as compared with the model group（P〈0.01）,but the difference was insignificant as compared with 5-Fu control group（P〈0.05）.CPUⅡover 10 mg·mL^-1had obvious inhibitory effect on the proliferation of HepG2 cells in vitro,and the effect was dose and time-dependent.CPUⅡover 2 mg·mL^-1had significant effect on inhibiting colony formation of HepG2 cells.After HepG2 cells were treated with CPUⅡat 10,15 mg·mL^-1for 48 hours,the percentage of HepG2 cells at G0/G1 phase was decreased and the percentage of HepG2 cells at S phase was increased significantly as compared with the model group（P〈0.01）.After HepG2 cells were treated with CPUⅡat 10,15,20mg·mL^-1for 48 hours,the early apoptotic rate and the overall apoptotic rate were increased obviously,and the difference was significant as compared with the model group（P〈0.01）.Wnt1 and β-catenin mR NA expression levels were obviously reduced in HepG2 cells treated with CPUⅡat 20,10 mg·mL^-1for 48 hours,the difference being significant compared with the model group（P〈0.05 or P〈0.01）.Conclusion CPUⅡ can effectively inhibit the growth of implanted