黄芪多糖对食管癌组织中炎症因子表达的影响及与p-AKT-AKT-VEGF信号通路的关系

Therapeutic effects and mechanism of ginseng polysaccharide on colon carcinoma and inflammatory factors via p-PKA-PKA-VEGF signaling pathway

目的观察黄芪多糖(astragalus polysaccharide,APS)对人食管癌(esophageal carcinoma,EPC)及癌旁组织(tissue adjacent of esophageal carcinoma,TAEC)中炎症因子表达的影响与AKT-VEGF信号通路间的关系.方法选取食管癌患者40例,其中20例作为药物治疗组(APS组),术前给予受试中药APS进行治疗7 d.另取EPC 20例,未进行APS药物辅助治疗,作为单纯手术治疗组(EPC组).术中收集手术切除的EPC肿瘤组织标本,另收集单纯手术组的EPC边缘外5 cm的癌旁标本20例作为空白对照组(TAEC组).采用酶联免疫吸附法(ELISA)测定炎症因子的含量变化,包括测定白细胞介素-2(IL-12)和白细胞介素-6(IL-6)及血管内皮生长因子(VEGF)的含量;另外,测定髓系细胞触发受体(triggering receptor expressed on myeloid cells-1,TREM-1)和表皮生长因子受体(epidermal growth factor receptor,EGFR)在EPC组织及癌旁组织中的表达情况.采用免疫组化方法,定位检测TREM-1及EGFR的阳性染色;采用Western blot方法检测AKT、p-AKT表达水平,以探讨APS对EPC作用的可能信号通路机制.结果给予APS后,与EPC组相比,患者术后一般状态明显改善.受试中药APS可显著降低炎症因子IL-12、IL-6及VEGF的含量,TREM-1及EGFR水平也明显减少(P<0.05).TREM-1及EGFR在TTEC中的阳性表达率高于EPC组(P<0.05).另外,APS能显著降低AKT蛋白表达,与EPC组比较,差异有统计学意义(P<0.05).结论传统中药APS可降低炎症因子表达,通过p-AKT-AKT-VEGF信号通路信号途径,发挥对EPC的辅助治疗作用.

Objective To investigate effects of astragalus polysaccharide(APS) on expression of inflammatory factors in esophageal carcinoma(EPC) tissues and tissue adjacent of esophageal carcinoma(TAEC) models, and the mechanism of AKT-VEGF. Methods In this study, 40 EPC patients were treated with APS for 7 days before operation. Another 20 cases of EPC were only treated with operation. During the operation, EPC intestinal specimens were collected and 20 adjacent tissue specimens were collected as TAEC control group. The levels of inflammatory factors, including interleukin-12(IL-12), IL-6 and VEGF, triggering receptor expression on myeloid cells-1(TREM-1) and epidermal growth factor receptor(EGFR) were measured by enzyme-linked immunosorbent assay(ELISA). The positive staining of TREM-1 and EGFR was detected by immunohistochemical method, and the expression levels of AKT and p-AKT were assessed by western blot. Results The general state of patients after APS treatment was improved compared with that of the simple operation group. APS could significantly reduce the levels of IL-12, IL-6, VEGF, TREM-1 and EGFR(P<0.05). The positive rates of TREM-1 and EGFR were significantly higher than those in TAC(P<0.05). In addition, APS could reduce the expression of AKT, which was significantly different from that of EPC group(P<0.05). Conclusion APS might reduce the inflammatory cytokines to protect cells from the EPC injury through the p-AKT-AKT-VEGF signal pathway.