黄芪-莪术配伍及联合顺铂对人肝癌裸鼠原位移植瘤生长的抑制作用

Inhibition Effects of Compatibility of Astragali Radix and Curcumae Rhizoma and Combination with Cisplatin on Orthotopic Tumor in Nude Mice Bearing Human Hepatocellular Carcinoma

摘要:

目的：探讨补气活血药黄芪-莪术配伍以及联合顺铂（DDP）对人肝癌裸鼠原位移植瘤生长的抑制作用。方法：构建人肝癌裸鼠原位移植瘤模型。成瘤后，将其随机分为8组：模型对照组、阳性对照组（DDP 2 mg·kg^-1，ip）、黄芪-莪术配伍高剂量组（H，12 g·kg^-1·d^-1，ig）、黄芪-莪术配伍中剂量组（M，6 g·kg^-1·d^-1，ig）、黄芪-莪术配伍低剂量组（L，3 g·kg^-1·d^-1，ig）、黄芪-莪术配伍高剂量+顺铂组（H+DDP）、黄芪-莪术配伍中剂量+顺铂组（M+DDP）、黄芪-莪术配伍低剂量+顺铂组（L+DDP），每组8只。观察黄芪-莪术配伍对原位移植瘤的作用及与DDP合用的效果；免疫组化SP法检测肿瘤组织缺氧诱导因子-1α（HIF-1α）、血管内皮生长因子（VEGF）的表达。结果：黄芪-莪术配伍H，M，L组的平均瘤重分别为 （1.28±0.21），（1.61±0.28），（1.65±0.27）g，平均瘤体积分别为 （1 065.42±275.63），（1 398.77±358.75），（1 419.28±405.17）mm³，均低于模型对照组的平均瘤重（2.19±0.30）g及平均瘤体积（1 866.21±433.49）mm³（P<0.05，P<0.01）；H+DDP，M+DDP，L+DDP的平均瘤重分别为（0.48±0.19），（0.83±0.29），（1.01±0.31）g，平均瘤体积分别为（381.86±273.14），（704.09±386.52），（827.75±424.58）mm³，均低于DDP组，H+DDP组有显著性差异（P<0.05）。免疫组化结果提示，黄芪-莪术配伍H，M，L，H+DDP，M+DDP，L+DDP各组HIF-1α，VEGF阳性表达强度均下降，与模型对照组比较有显著性差异（P<0.05，P<0.01）。结论：黄芪-莪术配伍对人肝癌裸鼠原位移植瘤的生长有抑制作用，且抑制作用与剂量有一定的正相关性，其机制可能与对HIF-1α，VEGF表达的抑制有关，与DDP合用表现为协同增效和相加作用。

Abstract:

Objective: To study the anti-tumor effects of Astragali Radix and Curcumae Rhizoma on the growth of transplanted human hepatocarcinoma in nude mice and its combinative effect with cisplatin(DDP). Method: Human hepatocarcinoma cells HepG2 were transplanted into nude mice to form the model, and the modeled mice were divided at random into 8 groups:model group, cisplatin(DDP) group (intraperitoneal injection with 2 mg·kg^-1 DDP), high dosage of Astragali Radix and Curcumae Rhisoma (H)(intragastric administration with 12 g·kg^-1·d^-1 physic liquor), intermediate dosage of Astragali Radix and Curcumae Rhizoma (M) (intragastric administration with 6 g·kg^-1·d^-1physic liquor), low dosage of Astragali Radix and Curcumae Rhizoma (L) (intragastric administration with 3 g·kg^-1·d^-1 physic liquor), high dosage and cisplatin group(H+DDP), intermediate dosage and cisplatin group(M+DDP), low dosage and cisplatin group(L+DDP), 8 in each group. The effect of Astragali Radix and Curcumae Rhizoma on Transplantation tumor and combinative effect with DDP were observed. Expressions of hypoxia inducible factor-1α (HIF-1α) and Wascular endothelial growth factor (VEGF) protein in transplantation tumors were determined by immunohisto chemical method with an image analysis system. Result: The tumor weight and volume were (1.28±0.21)g and (1 065.42±275.63)mm³ in H, (1.61±0.28)g and (1 398.77±358.75)mm³ in M, (1.65±0.27)g and (1 419.28±405.17)mm³ in L, all significantly lower than those in model group (2.19±0.30)g and (1 866.21±433.49)mm³, (P<0.05,P<0.01). The tumor weight and volume were (0.48±0.19)g and (381.86±273.14)mm³ in H+DDP, (0.83±0.29)g and (704.09±386.52)mm³ in M+DDP, (1.01±0.31)g and (827.75±424.58)mm³ in L+DDP.H+DDP group was significantly lower than DDP group(P<0.05). Contrary to the model group, expressions of HIF-1α and VEGF protein were significantly down-regulated by H, M, L, H+DDP, M+DDP and L+DDP group(P<0.05,P<0.01). Conclusion: Astragali Radix and Curcumae Rhizoma can inhibit the growth of human hepatocarcinoma in nude mice and the inhibition effect was positive correlation with dosage. The combination of Astragali Radix, Curcumae Rhizoma and DDP showed synergistic action and additive chemotherapeutic effect.