Background and purpose:Cyclooxygenase-2 (COX-2) participates in angiogenesis and lymph node metastasis of lung cancer. COX-2 inhibitors could inhibit invasion and metastasis of lung cancer. This study aimed to investigate the inhibition of invasion and metastasis by COX-2 inhibitor imrecoxib in xenograft tumor of lung adenocar-cinoma A549 cell in nude mice and to explore its possible mechanisms, in addition, to observe the efficacy of imrecoxib combined with lobaplatin.Methods:Thirty male BALB/c nude mice were injected subcutaneously with A549 cells into the right axillary region to establish xenograft models. Twenty-nine successfully modeled mice were randomly divided into four groups: control group (n=7), imrecoxib group (n=8), lobaplatin group (n=7), imrecoxib combined with lobaplatin group (n=7). The control group was treated with the same amount of sterile distilled water and injected with the same amount of 0.9% sodium chloride solution via caudal vein. The treatment group was treated with imrecoxib tablets 40 mg/kg per day through gavage and injected with lobaplatin 7.5 mg/kg per week via caudal vein respectively. The diet, physical activity and other normal conditions of nude mice were observed everyday. After 6 weeks, 29 mice were sacrificed and transplanted tumor tissues were cut off. The expression of PTEN, cortactin protein and mRNA were detected by immunohistochemistry and real-time PCR. The data were analyzed with one-way anova and non-parametric test.Results:In the last week, the diet and physical activity of all nude mice were less than before, and they became thinner, which were more obvious among the mice in lobaplatin group and imrecoxib combined with lobaplatin group. Compared with the control group, the expression of PTEN protein and mRNA were significantly increased in imrecoxib group and imrecoxib combined with lobaplatin group (P<0.001, respectively). Compared with the control group, the expression of cortactin protein and mRNA were significantly decreased in imrecoxib group and imrecoxib combined with lobaplatin group (P<0.001, respectively). PTEN and cortactin protein, PTEN and cortactin mRNA had significantly negative correlation (r=-0.660, -0.983,P<0.001, respectively). Conclusion:Imrecoxib can inhibit non-small cell lung cancer invasion and metastasis which may be involved in upregu-lating PTEN protein and reducing cortactin protein. Imrecoxib could enhance the effect of lobaplatin chemotherapy.

Objective To evaluate the inhibitory effect of imrecoxib combined with lobaplatin on tumor growth and lymph node metastasis of human lung adenocarcinoma xenografts in nude mice, and to explore its possible mechanisms. Methods Human lung cancer A549 cells were injected into Bal B/c nude mice subcutaneously. Twenty?eight healthy male nude mice were randomly divided into 4 groups:the control group, imrecoxib group, lobaplatin group and imrecoxib combined with lobaplatin group. Each group was treated with appropriate drugs and the tumor size was measured every five days. The expression of ezrin and E?cadherin protein was detected by immunohistochemistry and flow cytometry. Ezrin and E?cadherin mRNA were detected by real?time PCR. Results The tumor inhibition rates of imrecoxib group, lobaplatin group and combination group were 36.7%, 54.6% and 69.2%, respectively. The tumor volumes of imrecoxib group [(905.33±113.31) mm3] and combination group [(507.74±77.50) mm3] were significantly lower than that of the control group (1355.33±189.04) mm3(P<0.05), and the tumor weights were significantly reduced [(1.13±0.14) g, (0.63±0.10) g respectively] vs. (1.69±0.24) g (P<0.05). The expressions of ezrin protein and mRNA in the imrecoxib group and combined treatment group were significantly lower than that of the control group (136.53±35.52, 74.72±19.48 vs. 175.62±21.16 for protein expression level;0.54± 0.03, 0.36±0.03 vs. 1.02±0.02 for mRNA expression level, respectively, P<0.05 for both), while the expression of E?cadherin protein and mRNA in the imrecoxib group and combined treatment group was significantly higher than that of the control group ( 253. 78 ± 38. 87, 308. 94 ± 24. 67 vs. 213. 66 ± 30. 31 for protein expression level;2.19±0.02, 3.02±0.02 vs. 1.05±0.03 for mRNA expression level, respectively, P<0.05 for both) . There was a significant negative correlation between ezrin protein and E?cadherin protein (r=-0.737, P<0.01), as well as between ezrin mRNA and E?cadherin mRNA (r=-0.977, P<0.01). Conclusions Administration of imrecoxib combined with lobaphatin has inhibitory effects on the growth of non?small cell lung cancer xenografts and lymph node metastasis via down?regulated ezrin and upregulated E?cadherin. Imrecoxib and lobaplatin have a synergistic antitumor effect.

Objective To evaluate the inhibitory effect of imrecoxib combined with lobaplatin on tumor growth and lymph node metastasis of human lung adenocarcinoma xenografts in nude mice, and to explore its possible mechanisms. Methods Human lung cancer A549 cells were injected into Bal B/c nude mice subcutaneously. Twenty?eight healthy male nude mice were randomly divided into 4 groups:the control group, imrecoxib group, lobaplatin group and imrecoxib combined with lobaplatin group. Each group was treated with appropriate drugs and the tumor size was measured every five days. The expression of ezrin and E?cadherin protein was detected by immunohistochemistry and flow cytometry. Ezrin and E?cadherin mRNA were detected by real?time PCR. Results The tumor inhibition rates of imrecoxib group, lobaplatin group and combination group were 36.7%, 54.6% and 69.2%, respectively. The tumor volumes of imrecoxib group [(905.33±113.31) mm3] and combination group [(507.74±77.50) mm3] were significantly lower than that of the control group (1355.33±189.04) mm3(P<0.05), and the tumor weights were significantly reduced [(1.13±0.14) g, (0.63±0.10) g respectively] vs. (1.69±0.24) g (P<0.05). The expressions of ezrin protein and mRNA in the imrecoxib group and combined treatment group were significantly lower than that of the control group (136.53±35.52, 74.72±19.48 vs. 175.62±21.16 for protein expression level;0.54± 0.03, 0.36±0.03 vs. 1.02±0.02 for mRNA expression level, respectively, P<0.05 for both), while the expression of E?cadherin protein and mRNA in the imrecoxib group and combined treatment group was significantly higher than that of the control group ( 253. 78 ± 38. 87, 308. 94 ± 24. 67 vs. 213. 66 ± 30. 31 for protein expression level;2.19±0.02, 3.02±0.02 vs. 1.05±0.03 for mRNA expression level, respectively, P<0.05 for both) . There was a significant negative correlation between ezrin protein and E?cadherin protein (r=-0.737, P<0.01), as well as between ezrin mRNA and E?cadherin mRNA (r=-0.977, P<0.01). Conclusions Administration of imrecoxib combined with lobaphatin has inhibitory effects on the growth of non?small cell lung cancer xenografts and lymph node metastasis via down?regulated ezrin and upregulated E?cadherin. Imrecoxib and lobaplatin have a synergistic antitumor effect.