选择性COX-2抑制剂尼美舒利对人卵巢癌细胞株移植瘤生长的不同影响

Different effect of a selective cyclooxygenase-2 inhibitor on the growth of cell line of ovarian carcinoma xenografted tumor

目的:探讨选择性COX-2抑制剂尼美舒利(Nimesulide)对COX-2表达不同的人卵巢癌细胞株移植瘤生长的影响。方法:培养人卵巢癌细胞株SKOV-3(COX-2表达阴性)和OVCAR-3(COX-2表达阳性),制作裸鼠皮下移植瘤模型。应用尼美舒利干预,观察各组肿瘤的生长情况,绘制生长曲线,计算抑瘤率。测定移植瘤组织内血管内皮细胞生长因子(VEGF)含量。结果:SKOV-3组治疗组的肿瘤体积与对照组比较没有统计学差异(1.026 4±0.34)cm3vs(1.668 2±0.94)cm3(P=0.19>0.05);两组肿瘤的VEGF含量比较为没有统计学差异(1 481.1±235.61)pg/mL vs(1 648±179.02)pg/mL(P=0.09>0.05);两组的肿瘤生长曲线没有显著分离。OVCAR-3组治疗组的肿瘤体积(0.139 6±0.061)cm3小于对照组的肿瘤体积(0.263 4±0.056)cm3(P=0.01),抑瘤率为56.3%;治疗组的肿瘤生长曲线较对照组低平。治疗组肿瘤的VEGF含量为(1 070.4±578.29)pg/mL,低于对照组肿瘤的VEGF含量(1 641.3±541.84)pg/mL(P=0.04)。结论:选择性COX-2抑制剂对COX-2表达阳性的人卵巢癌组织有抑制生长的作用,对COX-2表达阴性的人卵巢癌组织的生长没有表现出抑制作用,这可能与COX-2抑制剂对COX-2表达不同的肿瘤组织内VEGF含量有不同的影响相关。

Objective：To evaluate the different effects of a selective COX-2 inhibitor nimesulide on the growth of cell line of ovarian carcinoma xenografted tumor. Methods：The cell lines SKOV-3 and OVCAR-3 were cultured in RPMI 1640,and the mice model was built by them. To measure the volume of tumors during the study,and draw the growth curve. The volume of tumors of nimesulide-group was compared with that of the control-group,and the vascular endothelial growth factor（ VEGF） levels in these tumors were measured. Results：SKOV-3 Group：Average tumor volume of control mice was（1. 668 2 ± 0. 94）cm3,and that of treated mice was（1. 026 4 ± 0.34）cm3.Therewasnodifferencebetweenthem（P=0.19〉0.05）.TheexpressionofVEGFwas（1481.1±235.61）pg/mLintrea-ted mice,while（1 648 ± 179. 02）pg/mL in control mice（P=0. 09〉0. 05）. The growth curves from two groups didn’t show the separate tendency.OVCAR-3Group：Averagetumorvolumeofcontrolmice（0.2634±0.056cm3）wasbiggerthanthat（0.1396±0.061cm3） of treated mice（P=0. 01〈0. 05）. The inhibitory rate of tumor growth is 56. 3%. Compared to control mice,the growth curve of treated mice was much lower and flatter. The expression of VEGF was significantly down regulated in the nimesulide-treated group：（1 070. 4 ± 578. 29 pg/mL）vs（1 641. 3 ± 541. 84 pg/mL）. Conclusion：The study implies that selective COX-2 inhibitors can inhibit COX-2-pos-tive tumor growth. There is no evidence to support that COX-2 inhibitors can inhibit COX-2-negative tumor. These findings might be cor-related with the treat-induced diversities of VEGF expression in different COX-2 profiles which lead to angiogenesis.