ANTITUMOR AND ANTIANGIOGENIC EFFECTS OF THALIDOMIDE, ROFECOXIB, AND CAPTOPRIL IN EHRLICH ASCITES CARCINOMA IN MICE

Abstract

The study was conducted to evaluate the effect of thalidomide, rofecoxib and captopril on tumor growth and survival, when used alone or in combinatiun with cisplatin in Swiss albino mice Solid tumors were induced by a subcutaneous injection of Ehrlich ascites carcinoma (EAC) Cells .The antiangiogenic activity of these drugs as studied to explore the potential mechanism involved. The EAC cells implanted subcutaneously to produce a solid tumor in the right flank of Swiss albino mice .This tumor was used to evaluate the anti-tumor and anti-angiogenic activities of thalidomide (100 mg/kg, i.p.) rofecoxib (20 mg/kg, p.o. ) or captopril(50 mg kg, p.o.)as individual treatments or in combination with cisplatin (2 mg/kg ,i.p.) All treatment, were started 24 hours after tumor cells inoculation .Tumor size was measured every other day for 21days, tumor growth time (TGT) and tumor growth delay time (TGDT) were calculated Animals were monitored and the mortality was recorded daily along the study period (100 days) to calculate the percentage survival of animals, mean survival time( MST) and percentage increased life span (%ILS).In a parallel experiment, the degree of angiogenesis was assessed by measuring the tumor vascular volume spectrophotometrically using 1% (w/v) Evan's blue. Individual treatments with thalidomide, rofecoxib or captopril produced a significant(p≤0.001) reduction in tumor volume as Compared to the control group. Their depressing effect on tumor volume tended to be enhanced progressively from the individual treatment to the combinations with cisplatin .The treatment with cisplatin, thalidomide and their combination could expand the life span of animals for 86,96 and 100 days respectively . Thalidomide and rofecoxib significantly (p≤0.05) inhibited the angiogenesis compared to the control group. The combination of cisplatin with thalidomide or rofecoxib further inhibited the angiogenesis significantly compared to the control group (p≤0.001) as well as cisplatin-treated group (p≤0.01). In the contrast, a significant inhibitory effect of captopril or cisplatin on angiogenesis was not evident. However, the combination of captopril and cisplatin could produce a significant inhibition of angiogenesis (p < 0.001). These data indicate that thalidomide, rofecoxib, or captopril exerts an antitumorigenic effect on EAC solid tumor in Swiss mice. Thalidomide and rofecoxib proved to have an antiangiogenic effect in EAC-model. Our results suggest the use of antiangiogenic agents as an adjuvant treatment to chemotherapy.