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Celecoxib 在人癌裸鼠移植瘤抗癌与放射增敏的作用机制研究

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

  • 摘要: 目的 探讨选择性环氧化酶-2 抑制剂celecoxib 抗癌及放射增敏作用的可能机制。方法 构建人宫颈癌裸鼠移植瘤模型,celecoxib 和/ 或移植瘤局部放射干预,检测移植瘤生长延缓、移植瘤组织中环氧化酶-2 与前列腺素E2 含量的变化,并分析此变化与移植瘤生长延缓的关系。结果 移植瘤最大径从8mm 生长至10mm 所需的时间,空白对照组为(4. 42 ±0. 78) d, 单纯放射组为(6. 25 ±0. 70) d, celecoxib组为(7. 14 ±1. 06) d, celecoxib + 放射联合组为(10. 62 ±2. 06) d ;Western Blot 显示4 组移植瘤组织中环氧化酶22 水平无明显差异;前列腺素E2 (pg/ 100mg) 含量分别为:空白对照组69. 07 ±5. 42, 单纯放射组47. 4 ±15. 94, 单纯celecoxib 组28. 62 ±4. 48, celecoxib + 放射联合组为43. 2 ±11. 73, 与空白对照组比较差异均有显著性( P = 0. 009 、0. 005 、0. 026) ;但celecoxib + 放射联合组与单纯放射组的前列腺素E2 含量无显著差异( P = 0. 28) ;celecoxib 引起的移植瘤生长延缓与前列腺素E2 含量降低正相关( r = 0. 741) 。结论 Celecoxib及移植瘤局部放射均能延缓移植瘤生长,不影响环氧化酶-2量的表达,但均能引起前列腺素E2 含量的降低;celecoxib 引起的移植瘤生长延缓可能与环氧化酶-2 活性被抑制后前列腺素E2 含量的降低有关。

     

    Abstract: 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.

     

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