关键词: 非小细胞肺癌, 侵袭转移, 艾瑞昔布, PTEN, 皮层肌动蛋白

Abstract: 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 adenocarcinoma 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 upregulating PTEN protein and reducing cortactin protein. Imrecoxib could enhance the effect of lobaplatin chemotherapy.

Key words: Non-small cell lung cancer, Invasion and metastasis, Imrecoxib, PTEN, Cortactin