Inhibitory effects of Celecoxib on Lewis lung carcinoma

Objective:To investigate the inhibitory effects of Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on the proliferation of Lewis lung carcinoma cell line and the growth of transplanted Lewis lung carcinoma in C_~57 BL/6 mice in vivo. Methods: The proliferation of Lewis lung carcinoma cells was measured by MTT assay. Flow cytometric analysis was used to detect cell apoptosis. The expression of vascular endothelial growth factor (VEGF) in Lewis lung carcinoma cell line was studied by enzyme-linked immunosorbent assay(ELISA). Twenty C_~57 BL/6 mice receiving tumor implantation were divided into 2 groups:food with 1 mg/g Celecoxib group and normal food group. Ultramicrostructure of Lewis lung carcinoma cells was observed under a transmission electron microscope(in 2 groups). The expressions of VEGF and COX-2 in xenografted tumor tissue were analyzed with immunohistochemical staining. Results: The proliferation of Lewis lung carcinoma cells was inhibited by Celecoxib in a dose and time-dependent manner. Flow cytometric analysis demonstrated that apoptosis cells of Lewis lung carcinoma were increased in Celecoxib-treated cells ([14.93±0.79]%) compared with those in the control group ([4.73±0.83]%)(P0.001). Celecoxib inhibited the growth of transplanted Lewis lung carcinoma significantly, with an inhibitory rate of ~60.1%. The subcutaneous tumor weight in the treated group and control group was (1.37±1.04) g and (3.49±1.75) g ~(P ~0.001), respectively. Typical apoptotic cells and apoptotic bodies were observed in the treated group under a transmission electron microscope. The VEGF staining score of tumor tissue in the treated group and control group was 2.00±0.82 and ~2.90± ~0.88 (P0.05), respectively. Conclusion: Celecoxib has inhibitory effect on Lewis lung carcinoma cells both in vitro and in vivo. Induction of apoptosis and antiangiogenesis might be the mechanism by which celecoxib exerts its chemopreventive and therapeutic effects.