The Mechanism of Celecoxib of Antitumor and Irradiation Enhancement Effects in Human Cervical Carcinoma Xenografts

Objective 　The antitumor and radiation-enhancement effect s of celecoxib, a selective of cyclooxygenase-2 inhibitors, in human cervical carcinoma xenograf t s had been described in one of our previous articles. The possible mechanisms of those effect s were investigated in this study. Methods 　The cyclooxygenase-2 enzyme was positive in HeLa cell line. Suspensions of HeLa cells were injected s. c. into the right thigh of BALB/ C female nude mice to make xenograf t s, and the xenograf t s were also cyclooxygenase-2 positive. The mice bearing tumors were divided into four groups : the cont rol group, the group with celecoxib alone, the group with radiation alone, the group combinated with both celecoxib and radiation. Each group consisted of 7 or 8 mice. The tumors were measured in the longest diameter everyday to calculate the tumor growth delay. Celecoxib and (or) 10 Gy single dose radiation were used to intervene the mice ; and, the tumor tissues were taken out to detect the changes of cyclooxygenase-2 protein level by Western blot and prostaglandin E₂ by radioimmuno-assay. Results 　The time that the longest diameters of all tumors grew from 8mm to 10mm were (4. 42 ±0. 78) d in the cont rol group, (6. 25 ±0. 70) d in the group with radiation alone, (7. 14 ±1. 06) d in the group with celecoxib alone, (10. 62 ±2. 06) d in the group combination both celecoxib and radiation. Analysis of variance showed that there was no significant difference in Cyclooxygenase-2 protein of tumors among these four groups. Prostaglandin E₂ levels (pg/ 100mg) of tumor tissues were 69. 07 ±5. 42, 28. 62 ±4. 48, 47. 4 ±15. 94, 43. 2 ±11. 73, respectively ( P = 0. 009, 0. 005, 0. 026, cont rast with cont rol group) . But prostaglandin E₂ levels in the group with radiation alone and in combination group had not significant difference ( P = 0. 28) . The tumor growth de-layed by celecoxib was directly correlated with the fall of prostaglandin E2 levels ( r = 0. 741) . Conclusion 　Cyclooxygenase-2 protein levels were not affected by celecoxib and 10 Gy single dose irradiation, but pros-taglandin E₂ levels decreased. The fall of prostaglandin E₂ may be a reason of the tumor growth delay by celecoxib.