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目的:观察表皮生长因子受体(EGFR)酪氨酸激酶抑制剂埃罗替尼与环氧合酶(COX-2)抑制剂塞来昔布对胆管癌荷瘤裸鼠的肿瘤生长协同抑制作用。方法:联合EGFR酪氨酸激酶抑制剂(EGFR-selective tyrosine kinaseinhibitor,EGFR TKI)埃罗替尼和COX-2抑制剂塞来昔布作用于胆管癌细胞株QBC939荷瘤裸鼠,评价药物体内作用效果。结果:埃罗替尼、塞来昔布联合用药显著抑制肿瘤生长,与对照组、埃罗替尼、塞来昔布单药组相比,均有显著性差异。抑制肿瘤生长的作用伴随EGFR下游活性蛋白p-MAPK的下调和VEGF、Ki-67表达的降低。肿瘤组织微血管密度降低。结论:埃罗替尼、塞来昔布抑制胆管癌荷瘤生长,抑制肿瘤细胞增殖,同时抑制肿瘤新生血管。两者具协同作用。靶向抑制EGFR和COX-2通路可以作为胆管癌的潜在治疗方法。
OBJECTIVE: To investigate the synergistic inhibitory effect of erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, and celecoxib, a cyclooxygenase (COX-2) inhibitor, on tumor growth in nude mice bearing cholangiocarcinoma. . METHODS: Combined with EGFR-selective tyrosine kinase inhibitor (EGFR TKI), erlotinib and COX-2 inhibitor celecoxib were administered to nude mice bearing cholangiocarcinoma cell line QBC939 to evaluate the effect of drugs in vivo. effect. RESULTS: The combination of erlotinib and celecoxib significantly inhibited tumor growth, and there were significant differences compared with the control group, erlotinib, and celecoxib monotherapy groups. The inhibition of tumor growth was accompanied by down-regulation of downstream active protein p-MAPK and decreased expression of VEGF and Ki-67. The density of microvessels in tumor tissue decreased. Conclusion: Erlotinib and celecoxib inhibit the growth of tumors in cholangiocarcinoma, inhibit the proliferation of tumor cells, and inhibit tumor neovascularization. Both have a synergistic effect. Targeted inhibition of EGFR and COX-2 pathways may serve as a potential treatment for cholangiocarcinoma.