山东医药2017,Vol.57Issue(15):13-16,4.DOI:10.3969/j.issn.1002-266X.2017.15.004
生长抑素14肽联合5-FU腹腔注射治疗人胃癌细胞裸鼠移植瘤的效果及机制
Effect of somatostatin 14 peptide combined with 5-FU by intraperitoneal injection on human gastric cancer xenografts in nude mice
摘要
Abstract
Objective To observe the effect of somatostatin-14 peptide (SST-14) combined with 5-fluorouracil (5-FU) by intraperitoneal injection on human gastric cancer BGC-823 xenografts in nude mice and to explore its mechanism. Methods We constructed 28 human gastric cancer cell line BGC-823 transplantation tumor models of nude mice, and randomly divided them into the control group, 5-Fu group, SST group and the combination group with 7 mice in each group. The combination group was treated with SST-14 and 5-FU, in which SST-14 was injected intraperitoneally 1 mg/kg for four days a week, stopped for three days; 5-FU was injected intraperitoneally 20 mg/kg one time per week. SST group was injected intraperitoneally with SST-14 (1 mg/kg) for four days a week, stopped for three days. 5-FU group was injected intraperitoneally with 5-FU (20 mg/kg) one time per week. The control group was given the same volume of sterile saline. Each group was treated for 21 d. The nude mice were killed by cervical dislocation at 24 h after the last medication. The tumor tissue was stripped completely.The tumor volume was measured and the tumor inhibition rate was calculated. TUNEL method was used to detect the apoptosis rate in the tumor tissues. The expression of Bcl-2 and Bax in tumor tissues was detected by immunohistochemical SP method, and pERK and ERK was detected by Western blotting. Results The tumor volume of 5-FU group, SST group and the combination group was less than that of the control group after treatment, and the tumor volume of the combination group was less than that of 5-FU group and SST group (all P<0.05). The inhibition rate of tumor volume was 26.243% in the 5-Fu group, 25.447% in the SST group, and 44.433% in the combination group. The apoptosis rate in the 5-FU group, SST group and the combination group was higher than that of the control group, and the apoptosis rate in the combination group was higher than that in the 5-FU group and SST group (all P<0.05). Compared with the control group, Bcl-2 protein expression and Bcl-2/Bax in transplanted tumor tissues decreased, Bax protein expression increased in the 5-FU group, SST group and the combination group (all P<0.05). Compared with 5-FU group and SST group, the relative expression level of Bcl-2 protein and Bcl-2/Bax decreased, but the relative expression level of Bax protein increased in the combination group (all P<0.05). The expression of pERK protein of the SST group and the combination group was lower than that of the control group (P<0.05). Conclusions SST-14 combined with 5-FU by intraperitoneal injection can inhibit the growth of human gastric cancer BGC-823 xenografts in nude mice, promote apoptosis of gastric cancer cells, and the effect is better than that of SST-14 or 5-FU alone. The mechanism may be related to the down-regulation of pERK expression in gastric cancer cells by SST-14.关键词
胃癌/胃癌细胞/移植瘤/生长抑素14/5-氟尿嘧啶/细胞凋亡/细胞外信号调节激酶Key words
gastric carcinoma/gastric carcinoma cells/xenografts/somatostatin-14/5-fluorouracil/apoptosis/extracellular signal-regulated kinase分类
医药卫生引用本文复制引用
封安强,张南征..生长抑素14肽联合5-FU腹腔注射治疗人胃癌细胞裸鼠移植瘤的效果及机制[J].山东医药,2017,57(15):13-16,4.基金项目
南京军区医学科技创新项目(15ms044). (15ms044)