苦参素辅助化疗对肝癌腹水荷瘤小鼠的抗肿瘤作用

Anti-tumor effect of marine adjuvant chemotherapy in hepatoma ascites tumor-bearing mice

目的探讨苦参素辅助化疗对肝癌腹水荷瘤小鼠抗肿瘤作用及对磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(Akt)通路的调控机制。方法除对照组,各组制备H22肝癌腹水荷瘤小鼠模型。苦参素组腹腔注射200 mg·kg^(-1)苦参素,环磷腺苷(CTX)组腹腔注射30 mg·kg^(-1) CTX,CTX+苦参素组腹腔注射200 mg·kg^(-1)苦参素和30 mg·kg^(-1)CTX溶液,模型组和对照组腹腔注射等量生理盐水,连续14 d。比较各组抑瘤率、肿瘤细胞凋亡率、肿瘤组织中PI3K/Akt通路相关基因和蛋白表达量。结果苦参素组、CTX组和CTX+苦参素组抑瘤率分别为(35.64±5.15)%,(64.60±5.60)%,(75.17±6.21)%,差异有统计学意义(P<0.05)。与模型组、苦参素组、CTX组和CTX+苦参素组肿瘤细胞凋亡率分别为(5.18±1.44)%,(23.75±2.50)%,(39.08±3.65)%,(47.55±3.92)%,差异均有统计学意义(均P<0.05)。与模型组比较,苦参素组、CTX组及CTX+苦参素组PI3K mRNA和蛋白相对表达量及p-Akt/Akt均降低,其中CTX+苦参素组低于苦参素组和CTX组(P<0.05);与模型组比较,苦参素组、CTX组及CTX+苦参素组Caspase3 mRNA和蛋白相对表达量均升高,其中CTX+苦参素组高于苦参素组和CTX组(均P<0.05)。结论苦参素协同增强化疗抗肿瘤效果,且能提高荷瘤鼠免疫功能,其机制可能与抑制PI3K/Akt通路激活有关。

Objective To investigate the anti-tumor effect of marine adjuvant chemotherapy on liver cancer and ascites tumor-bearing mice and its regulation mechanism on phosphatidylinositol-3 kinase(PI3 K)/protein kinase B(Akt) pathway. Methods Except control group, the remaining groups were prepared H22 liver cancer ascites tumor-bearing mouse models. The matrine group was intraperitoneally injected with 200 mg·kg^(-1) marine, cyclophosphamide(CTX) group was intraperitoneally injected with 30 mg·kg^(-1) CTX, CTX+marine group was injected with 200 mg·kg^(-1) marine and 30 mg·kg^(-1) CTX solution. Model group and control group were intraperitoneally injected with the same amount of normal saline for 14 d. Tumor inhibition rate, tumor cell apoptosis rate, PI3 K/Akt pathway related gene and protein expression in tumor tissues were compared in each group. Results The tumor inhibition rates in marine group, CTX group and CTX+marine group were(35.64±5.15)% ( 64. 60 ± 5. 60) %,( 75. 17 ± 6. 21) %,with significant difference( P < 0. 05). The tumor cell apoptosis rates in model group,marine group,CTX group and CTX + marine group were( 5. 18 ± 1. 44) %,( 23. 75 ± 2. 50) %,( 39. 08 ± 3. 65) % and( 47. 55 ± 3. 92) %,all with significant difference( all P < 0. 05). Compared with model group,the relative expressions of PI3 K mRNA and protein and p-Akt/Akt in matrine group,CTX group and CTX +marine group were all decreased,and CTX + marine group was lower than marine group and CTX group( all P < 0. 05). Compared with model group,the relative expressions of Caspase3 mRNA and protein in marine group,CTX group and CTX + marine group were all increased,and the CTX + marine group was higher than marine group and CTX group( all P < 0. 05). Conclusion Marinee synergistically enhances the anti-tumor effect of chemotherapy and can improve the immune function of tumor-bearing mice. The mechanism may be related to the inhibition of PI3 K/Akt pathway activation.