重组东亚钳蝎镇痛抗肿瘤肽协同5-氟尿嘧啶对小鼠H22肝癌的抑制作用

Inhibition of recombinant analgesic-antitumor peptide combined with 5-flurouracil on H22 hepatoma in mice

目的:探讨重组东亚钳蝎镇痛抗肿瘤肽(recombinant analgesic-antitumor peptide,r AGAP)增强5-氟尿嘧啶(5-fluorouracil,5-FU)对肝癌H22细胞的抑制作用及机制。方法:SPF级雄性小鼠120只,采用接种H22肝癌小鼠腹水方法建立模型,随机分为4组:r AGAP组(予r AGAP 0.03 mg/kg)、5-FU组(予5-FU 10 mg/kg)、联合组(予r AGAP 0.03 mg/kg,5-FU 10 mg/kg),模型组(予等体积生理盐水),每4 d腹腔注射1次,用药持续24 d。用药结束后取出肿瘤组织标本,检测各组瘤体组织重量和抑瘤率,Western blot方法检测PI3K、AKT、PTEN蛋白表达。结果:与模型组相比,其他各组小鼠瘤体组织重量均明显降低(P<0.05);联合组抑瘤率明显高于r AGAP组和5-FU组(P<0.05)。与模型组相比,其他各组PI3K、p-Akt表达均明显减弱,PTEN表达明显增强(P<0.05);与5-FU组、r AGAP组相比,联合组PI3K、p-Akt表达均明显减弱,PTEN表达明显增强(P<0.05)。结论:r AGAP能增强5-FU对肝癌组织的抑制作用,其机制可能与影响PI3K/AKT/PTEN信号通路,进而抑制肝癌细胞的增殖有关。

Objective： To investigate the inhibitory effect and mechanism of recombinant analgesic-antitumor peptide （rAGAP） enhanced 5-fluorouracil （5-FU） on H22 hepatoma. Methods： The models of H22 hepatoma in mice were established through ascites inoculating H22 cells suspension into mice in right armpits, and randomly divided into 4 groups, rAGAP group was given 0.03 mg/kg IP rAGAP, 5-FU group 10 mg/kg IP 5-FU, United group 0.03 mg/kg 5-FU and 10 mg/kg IP rAGAP, Model group used equal volume of normal saline intraperitoneal injection for 3 weeks. After that, the tumor tissue were sampled, the tumor weight and tumor inhibition rate were detected. The expressions of PI3K, AKT, and PTEN were detected by Western blot method. Results： Compared with Model group, mice tumor weight of other groups was significantly lower （P〈0.05）; tumor suppressor rate of United Group was obviously higher than that of rAGAP group and 5-FU group （P〈0.05）. Compared with Model group, PI3K and p-Akt expression of other groups were significantly decreased, but PTEN expression was significantly increased （P〈0.05）; compared with 5-FU group, rAGAP group, PI3K and p-Akt expression of United group were significantly reduced, but PTEN expression was significantly increased （P〈 0.05）. Conclusion： rAGAP can enhance the inhibitory effect of 5-FU on H22 hepatoma, its mechanism may be related to the activity of PI3K/AKT/PTEN signaling pathway, and then inhibition the proliferation of H22 hepatoma.