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目的探讨厄洛替尼和塞来昔布联合阻断表皮生长因子受体(EGFR)和环氧合酶-2(COX-2),对人肺腺癌裸鼠移植瘤生长及血管形成的影响。方法人肺癌细胞A549接种于裸鼠皮下,成瘤后随机分为4组:对照组、厄洛替尼组、塞来昔布组、塞来昔布和厄洛替尼联合用药组,给予灌胃处理,观察裸鼠生长状况,每周两次测量肿瘤大小,绘制肿瘤生长曲线。40 d后处死裸鼠,称取移植瘤质量。采用免疫组化检测肿瘤微血管密度(MVD),ELISA法检测裸鼠血清中血管内皮生长因子(sVEGF)的含量,Western Blot法检测Bcl-2、Bax蛋白的表达情况并计算Bcl-2/Bax的值。结果联合用药组肿瘤明显小于塞来昔布组、厄洛替尼组和对照组(P<0.05)。联合用药组微血管数目、sVEGF的含量明显小于塞来昔布组、厄洛替尼组和对照组(P<0.05)。厄洛替尼组Bcl-2的表达明显小于对照组(P<0.05),塞来昔布组Bcl-2的表达与对照组相比差异无统计学意义(P>0.05),联合用药组Bcl-2的表达与对照组、塞来昔布组、厄洛替尼组相比均明显降低(P<0.05)。Bax的表达在各组之间差异无统计学意义(P>0.05)。联合用药组Bcl-2/Bax较塞来昔布组、厄洛替尼组明显降低(P<0.05)。结论塞来昔布联合厄洛替尼相对厄洛替尼或塞来昔布明显抑制人肺癌移植瘤的生长。其中减少微血管生成、增加肿瘤细胞的凋亡可能为其抗肿瘤机制。
Objective To investigate the effects of erlotinib and celecoxib on the growth and angiogenesis of human lung adenocarcinoma xenografts in nude mice by blocking the combination of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) . Methods Human lung adenocarcinoma A549 cells were subcutaneously inoculated into nude mice and were randomly divided into 4 groups: control group, erlotinib group, celecoxib group, celecoxib group and erlotinib group. Stomach treatment, observe the growth of nude mice, tumor size was measured twice a week, the tumor growth curve was drawn. After 40 days, the nude mice were sacrificed and the quality of the transplanted tumor was weighed. Tumor microvessel density (MVD) was detected by immunohistochemistry. The level of sVEGF in serum was detected by ELISA. The expression of Bcl-2 and Bax was detected by Western Blot. value. Results The tumor volume in combination group was significantly lower than that in celecoxib group, erlotinib group and control group (P <0.05). Compared with the celecoxib group, the erlotinib group and the control group, the number of microvessel and sVEGF in the combination group was significantly (P <0.05). The expression of Bcl-2 in erlotinib group was significantly lower than that in control group (P <0.05), while there was no significant difference in Bcl-2 expression between celecoxib group and control group (P> 0.05) -2 was significantly lower than that of control group, celecoxib group and erlotinib group (P <0.05). There was no significant difference in the expression of Bax among the groups (P> 0.05). Bcl-2 / Bax in combination group was significantly lower than that in celecoxib group and erlotinib group (P <0.05). Conclusion The combination of celecoxib and erlotinib against erlotinib or celecoxib significantly inhibits the growth of human lung cancer xenografts. Which reduce the micro-angiogenesis and increase the apoptosis of tumor cells may be its anti-tumor mechanism.