Abstract:

Abstract:Objective To investigate the inhibitory effects and possible anticarcinogenic mechanism of celecoxib on the proliferation of Lewis lung carcinoma cells in vitro and in vivo.Methods The proliferation of Lewis lung carcinoma cells　treated with different doses (50,100 and 200  μmol?L-1) of celecoxib for 12,24,48 and 72 h,was measured by MTT assay.The contents  of arachidonic acid and prostaglandin E2 in the culture supernatants at 24 h were measured by the methods of RP-HPLC and PGE2-specific ELISA respectively.Twenty C57BL/6 mice receiving tumor implantation were divided randomly into control group and treatment(200 mg•kg^-1) groups. All the groups were gavaged continuously with normal saline or celecoxib on the third day after implantation.The mice were killed on the 15th day,and the volume and weight of the tumor tissues were calculated.Results Compared with control group,50,100 and 200 μmol•L^-1 celecoxib inhibited the proliferation of Lewis cells (P<0.05),the inhibitory rate was  increased with the dose and time of treatment.The IC50 value of 72 h was (134.06±2.97)  μmol•L^-1.Compared with control group,celecoxib had no effect on the arachidonic acid content,but depressed the prostaglandin E2 level in the culture supernatants in 50  μmol•L^-1 treatment group (P<0.05). In 100 and 200  μmol•L^-1　 treatment groups,celecoxib  significantly increased the content of arachidonic acid and depressed the prostaglandin E2 level in the culture supernatants with the  increasing of the  dose  of celecoxib (P<0.01). The solid tumor volume and weight in treatment group were lower than those in control group (P<0.05), and the tumor inhiitory rate in treatment group was 50%.Conclusion Celecoxib can inhibit the growth of Lewis lung carcinoma cells in vitro and in vivo.The anticarcinogenic effect of celecoxib depends on not only increasing the prodcution of arachidonic acid,but also inhibiting the synthesis of prostaglandin E2 in Lewis lung carcinoma treated with celecoxib.

Key words: celecoxib;carcinoma,lewis lung;arachidonic acid;prostaglandin E2