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目的观察表皮生长因子受体抑制剂埃罗替尼对胰腺癌新生血管生成的影响,探讨其对胰腺癌生长抑制的作用机制。方法①应用小管形成实验观察埃罗替尼(终浓度100μmol/L)对血管生成的影响,并与对照组(加入无血清培养液)进行比较。②建立胰腺癌细胞株BxPC-3裸鼠移植瘤模型,用埃罗替尼灌胃,每天100 mg/kg,共4周。每周测量移植瘤体积,4周后处死裸鼠,计算抑瘤率,并与未用埃罗替尼对照组裸鼠比较。RT-PCR法检测不同浓度(5、50、100、200μmol/L)埃罗替尼处理后BxPC-3细胞血管内皮生长因子(VEGF)表达的变化。采用Ⅷ因子免疫组化染色评估瘤组织中微血管密度(MVD)。结果小管形成实验中,埃罗替尼组细胞数显著少于对照组,中空闭合管状结构缺如。埃罗替尼灌胃4周后,治疗组平均瘤重(0.397±0.550)g,显著低于对照组的(1.570±1.060)g,抑瘤率为74.5%。浓度≥50μmol/L的埃罗替尼各组BxPC-3细胞中VEGF mRNA相对表达量较对照组下调,移植瘤组织VEGF表达亦较对照组显著下调.瘤组织MVD(1.86±0.43)显著低于对照组(5.98±1.27,P<0.01)。结论埃罗替尼可抑制裸鼠移植瘤生长和胰腺癌体内、体外血管的生成,可作为胰腺癌的辅助治疗方法之一。
Objective To observe the effect of erlotinib, an inhibitor of epidermal growth factor receptor, on neovascularization of pancreatic cancer and to explore its mechanism of action on the growth of pancreatic cancer. Methods ① The effect of Erlotinib (final concentration 100 μmol / L) on angiogenesis was observed by the tubule formation experiment and compared with the control group (with serum-free medium). (2) To establish pancreatic cancer cell line BxPC-3 xenografted tumor model in nude mice by intragastric administration with erlotinib 100 mg / kg daily for 4 weeks. The volume of tumor xenografts was measured every week. After 4 weeks, the nude mice were sacrificed and the tumor inhibition rate was calculated. Compared with the non-erlotinib control group, the nude mice were compared. The expression of vascular endothelial growth factor (VEGF) in BxPC-3 cells treated with different concentrations of Erlotinib (5, 50, 100, 200μmol / L) was detected by RT-PCR. The Ⅷ-factor immunohistochemistry was used to evaluate the microvessel density (MVD) in tumor tissue. Results In the tube formation experiment, the number of cells in the erlotinib group was significantly less than that in the control group, and the absence of a hollow closed tubular structure. The average tumor weight (0.397 ± 0.550) g in the treatment group was significantly lower than that in the control group (1.570 ± 1.060) g after the erlotinib treatment for 4 weeks, with a tumor inhibition rate of 74.5%. The relative expression of VEGF mRNA in Erlotinib-treated BxPC-3 cells was lower than that in control group at a concentration of ≥50μmol / L, and the VEGF expression was significantly down-regulated in xenograft tumor tissues compared with the control group (MVD = 1.86 ± 0.43) Control group (5.98 ± 1.27, P <0.01). Conclusion Erlotinib can inhibit the growth of xenograft tumors and the formation of in vitro and in vivo blood vessels in pancreatic cancer, which may be used as adjuvant therapy for pancreatic cancer.