目的 探討艾瑞昔布聯(lián)合5-氟尿嘧啶（5-Fu）對結(jié)腸癌HT-29細胞裸鼠移植瘤侵襲和轉(zhuǎn)移的影響以及與環(huán)氧化酶-2（COX-2）、血管內(nèi)皮生長因子-C（VEGF-C）、基質(zhì)金屬蛋白酶-9（MMP-9）的關(guān)系。方法 40只裸鼠構(gòu)建人結(jié)腸癌HT-29細胞裸鼠皮下移植瘤模型，隨機分為4組，每組10只，對照組（0.9% NaCl）；艾瑞昔布組［100 mg/（kg·d）］；5-Fu組（20 mg/kg）；聯(lián)合用藥組［艾瑞昔布100 mg/（kg·d），5-FU 20 mg/kg］，艾瑞昔布ig給藥，1次/d，5-Fu ip給藥，每3天1次，連續(xù)給藥14 d。實驗結(jié)束時測量各組裸鼠瘤體大小，并計算抑瘤率；酶聯(lián)免疫吸附試驗（ELISA）檢測COX-2、VEGF-C、MMP-9血清濃度，實時熒光定量PCR（qRT-PCR）檢測COX-2、VEGF-C、MMP-9的mRNA表達，免疫組化法檢測瘤體微血管密度（MVD），Western blotting法檢測COX-2、VEGF-C、MMP-9蛋白表達。結(jié)果 艾瑞昔布組、5-Fu組、聯(lián)合用藥組與對照組比較，抑瘤效果顯著，其中以聯(lián)合用藥組抑瘤效果最佳（P<0.05）。艾瑞昔布組、5-Fu組、聯(lián)合用藥組較對照組裸鼠血清COX-2、VEGF-C、MMP-9濃度、瘤體COX-2、VEGF-C、MMP-9的mRNA和其蛋白表達、瘤體MVD均顯著降低（P<0.05），其中以聯(lián)合用藥組降低最顯著（P<0.05）。結(jié)論 艾瑞昔布聯(lián)合5-Fu可協(xié)同抑制結(jié)腸癌裸鼠移植瘤侵襲和轉(zhuǎn)移，增強5-Fu的抗腫瘤效果，其作用機制可能與下調(diào)COX-2、VEGF-C、MMP-9表達有關(guān)。

Objective To investigate the effect of ericoxib combined with fluorouracil on the invasion and metastasis of colon cancer HT-29 cells in nude mice, and with cyclooxygenase-2 (COX-2), vascular endothelial growth factor-C (VEGF-C), matrix metalloprotein-9 (MMP-9) relationship. Methods Forty nude mice were used to construct a subcutaneous xenograft model of human colon cancer HT-29 cells in nude mice. Model nude mice were randomly divided into 4 groups, 10 mice in each group. Four groups were control group (0.9% Nacl), ericoxib group [ericoxib 100 mg/(kg.d)], fluorouracil group (5-Fu 20 mg/kg), and combination group [ericoxib 100 mg/(kg.d), 5-Fu 20 mg/kg]. Ericoxib was administered by intragastrically, once daily, 5-Fu was administered by intraperitoneal injection, once 3 days, continuous administration for 14 days. Tumor size were measured and of tumor inhibition rate were calculated at the end of the experiment. Enzyme linked immunosorbent assay (ELISA) was used to detect concentrations of COX-2, VEGF-C and MMP-9 in serum of nude mice. mRNA expression of COX-2, VEGF-C and MMP-9 were detected by Real-time quantitative PCR (Real-time PCR). MVD of tumor was detected by immunohistochemical method. COX-2, VEGF-C and MMP-9 protein expression were analyzed by Western blotting. Results Compared with the control group, the tumor inhibition effect of the ericoxib group, the fluorouracil group and the combination group were remarkable, and the anti-tumor effect was the best in the combination group (P<0.05). Compared with the control group, COX-2, VEGF-C, MMP-9 concentrations in serum, mRNA and protein expression of tumor COX-2, VEGF-C, MMP-9, tumor MVD of nude in the ericoxib group, fluorouracil group, and combination group were reduced. Among them, anti-tumor effect of the combination group was the most significant (P<0.05). Conclusion Erexib combined with fluorouracil can synergistically inhibit the invasion and metastasis of human colon cancer xenografts in nude mice, and enhance the anti-tumor effect of fluorouracil. The mechanism may be related to the down-regulation of COX-2, VEGF-C and MMP-9 expression.

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