目的 研究苦參堿對人肝癌細(xì)胞HepG2荷瘤裸鼠的抑瘤作用及其作用機(jī)制。方法 BALB/C裸鼠隨機(jī)分為對照組和苦參堿25、50、75 mg/kg組,每組各10只。建立裸鼠肝癌細(xì)胞HepG2移植瘤模型。對照組ip生理鹽水1 mL,1次/d;苦參堿25、50、75 mg/kg組分別ip 0.5、1.0、1.5 mg/mL苦參堿溶液1 mL,1次/d。連續(xù)給藥35 d。計算瘤體體積和腫瘤體積抑制率。觀察裸鼠瘤體HE染色病理改變和免疫組化染色,測定各組裸鼠瘤體Survivin蛋白表達(dá)量,并采用RT-PCR法檢測裸鼠瘤體Survivin mRNA相對表達(dá)量。結(jié)果 與對照組比較,苦參堿50、75 mg/kg組裸鼠瘤體體積顯著減小(P<0.01);苦參堿組裸鼠瘤體生長速度較對照組減慢,肝癌細(xì)胞分布較對照組稀疏,且劑量越大越明顯?？鄥A50、75 mg/kg組僅有少量Survivin表達(dá)于細(xì)胞質(zhì)。與對照組比較,苦參堿50、75 mg/kg組裸鼠Survivin蛋白表達(dá)量和Survivin mRNA相對表達(dá)量顯著減小(P<0.01)。結(jié)論 苦參堿對人肝癌細(xì)胞HepG2荷瘤裸鼠具有抑瘤作用,有效劑量為50 mg/kg,其機(jī)制可能與下調(diào)Survivin表達(dá)、誘導(dǎo)肝癌細(xì)胞凋亡有關(guān)。

Objective To study the anti-tumor effect of matirine on human hepatocarcinoma cell line HepG2 implanted tumor in nude mice and explore its mechanism. Methods BALB/C nude mice were randomly divided into the control group and the matirine (25, 50, and 75 mg/kg) groups, and each group had 10 mice. Human hepatic cancer cells HepG2 were planted into BALB/C nude mice to establish the cancer models of HepG2. Mice in the control group were ip administered with normal saline 1 mL and those in the matirine groups were ip administered with 0.5, 1.0, and 1.5 mg/mL matirine solution 1 mL All mice were ig administered once daily, and treated for 35 d. Volume of implanted tumor and inhibitory rate were calculated. Pathological changes of the tumors with HE staining and SP staining were observed. Expression of Survivin was evaluated, and relative expression of Survivin mRNA of tumor in nude mice were determined by RT-PCR method. Results Compared with the control group, volumes of the implanted tumor in the matirine (50 and 75 mg/kg) groups were significantly decreased (P < 0.01). Compared with the control group, the growth speeds of tumor in the matirine groups were slower, liver cancer cell distributions were lager in dose-dependent manner, and small amounts of Survivin were expressed in the cytoplasm in the matirine (50 and 75 mg/kg) groups. Compared with the control group, expression of Survivin and relative expression of Survivin mRNA of tumor in the matirine (50 and 75 mg/kg) groups were significantly decreased (P < 0.01). Conclusion Matirine has anti-tumor effect on human hepatocarcinoma cell HepG2 tumor in nude mice with effective dose of 50 mg/kg, which may be attributed to down-regulate the expression of Survivin and inducing the apoptosis of hepatocellular carcinoma cells.

國家自然科學(xué)基金資助項目(30772859)