莪术醇联合氟尿嘧啶对裸鼠胃癌移植瘤生长、增殖细胞核抗原和P27表达的影响

Effect of curcumol combined with fluorouracil on growth of gastric cancer implantation tumor in nude mice and expressions of PCNA and P27 genes

摘要:

目的  观察莪术醇联合氟尿嘧啶对胃癌裸鼠皮下移植瘤的影响。方法  将人胃癌细胞株BGC823接种于裸鼠皮下建立荷瘤裸鼠模型。将荷瘤裸鼠随机分为对照组、莪术醇组、氟尿嘧啶组、联合用药组（莪术醇联合氟尿嘧啶），记录各组的肿瘤体积和瘤重。应用荧光定量聚合酶链反应（qPCR）和免疫组织化学法检测各组肿瘤组织中增殖细胞核抗原（PCNA）、P27的表达。结果  对照组肿瘤体积和重量比其他3组升高（P <0.05）；联合用药组肿瘤体积和重量低于莪术醇组（P <0.05）；联合用药组肿瘤体积和重量与氟尿嘧啶组比较，差异无统计学意义（P >0.05）。各实验组肿瘤组织中PCNA的表达均低于对照组（P <0.05）；与莪术醇组和氟尿嘧啶组比较，联合用药组PCNA的表达降低（P <0.05）。各实验组移植瘤组织中P27的表达均高于对照组（P <0.05）；与莪术醇组比较，联合用药组P27的表达增强（P <0.05）；与氟尿嘧啶组比较，联合用药组P27 mRNA的相对表达有升高趋势，但差异无统计学意义（P >0.05）。与莪术醇组和氟尿嘧啶组比较，联合用药组P27蛋白阳性率升高（P <0.05）。结论  莪术醇联合氟尿嘧啶能抑制胃癌裸鼠皮下移植瘤的生长，其机制可能与调节PCNA、P27基因有关。

关键词:

莪术醇;胃癌;裸鼠皮下移植瘤;增殖细胞核抗原;P27

Abstract:

Objective To observe the effect of curcumol combined with fluorouracil (FU) on subcutaneous transplantation tumor tissues of gastric cancer cells in nude mice. Methods The implantation tumor model was built by subcutaneous inoculation of human gastric cancer cell line BGC823 in nude mice. The tumor-bearing mice were randomly divided into control group, curcumol group, FU group and combination group (curcumol combined with FU). Data of tumor volume and weight of each group were collected. Expressions of PCNA and P27 genes in tumors of the 4 groups were detected with qPCR and immunohistochemistry. Results The tumor volume was significantly smaller and the tumor weight was significantly lower in the 3 experimental groups than in the control group (P < 0.05). Compared with the curcumol group, the tumor volume was significantly smaller  and the tumor weight was significantly lower in the combined group (P < 0.05). The volume and weight of the tumors had no significant diffe-rences between the FU group and the combined group (P > 0.05). The expression of the PCNA in the experimental groups was significantly lower than that in the control group (P < 0.05). Compared with the curcumol group and the FU group, the expression of PCNA in tumor tissues of the combined group significantly decreased (P < 0.05). The expression of the P27 in the 3 experimental groups was significantly higher than that in the control group (P < 0.05). Compared with the curcumol group, the expression of P27 in the combined group significantly increased (P < 0.05). There was no significant difference in P27 mRNA of tumor tissues between the combined group and the FU group (P > 0.05). The positive percentages of p27 protein in the 3 experiment groups were significantly higher than that in the control group (P < 0.05). Compared with the curcumol group and the fluorouracil group, the positive percentages of PCNA protein in the combined group was significantly higher (P < 0.05). Conclusions Curcumol combined with FU could inhibit the growth of  subcutaneous transplantation tumor of human gastric cancer cells in nude mice, which might be related to regulation of PCNA and P27 genes.

Key words:

curcumol; gastric cancer; subcutaneous transplantation tumor of nude mice; proliferating cell nuclear antigen; P27