选择性环氧化酶-2抑制剂联合放疗对人前列腺癌裸鼠移植瘤作用的实验研究

目的研究选择性环氧化酶-2（COX-2）抑制剂塞来昔布（celecoxib）对前列腺癌的抗肿瘤作用和放疗增敏效应,并探讨其协同抑制作用的机制。方法使用前列腺癌PC-3细胞构建人前列腺癌裸鼠移植瘤模型,将荷瘤裸鼠随机分为对照组、celecoxib组、放疗组和celecoxib联合放疗组4组,每组6只。观察移植瘤的肿瘤生长延缓时间（TGD）和增敏系数（EF）;放射免疫法（ELISA法）测定前列腺素E2（PGE2）的含量,逆转录-聚合酶链反应（RT-PCR法）检测移植瘤组织中COX-2mRNA的表达,并观察荷瘤鼠各重要脏器组织的病理学改变。结果对照组和celecoxib组中移植瘤最大径从8.0mm生长至12.0mm所需的时间分别为（6.18±0.72）d和（7.87±0.76）d,而放疗组和celecoxib联合放疗组分别为（9.16±0.89）d和（12.62±1.28）d,组间差异有统计学意义（P〈0.05）,EF为1.59;对照组与其余3组间的PGE：含量差异均有统计学意义（P〈0．05），而放疗组与celecoxib联合放疗组间PGE2含量差异无统计学意义（P〉0．05）；celecoxib引起的生长延缓与PGE：含量的下降呈正相关（r=0．807）；4组移植瘤组织中COX一2mRNA表达水平差异均无统计学意义（P〉0．05）；各组荷瘤鼠重要脏器未发现明显毒性病理学改变。结论Celecoxib联合放疗治疗人前列腺癌裸鼠皮下移植瘤具有抗肿瘤作用和放射增敏效应，可发挥协同抑制作用，在一定范围内是安全有效的，这为今后的前列腺癌的研究和临床治疗提供了一定的思路。

Experimental Study on Selective Cyclooxygenase-2 Inhibitor Combined with Radiotherapy for Human Prostate Carcinoma Xenografts in Nude Mice

Objective To investigate the anti-tumor and radiation-enhancement effects and observe a coordinate repression of celecoxib, a selected cyclooxygenase-2 inhibitor in prostate carcinoma. Methods An animal model of human prostate carcinoma in BALC/C male nude mice was establised by injecting suspension of PC-3 cells and the mice were randomly divided into 4 groups which were inter- fered with celecoxib, radiation, and both celecoxib and radiation respectively, with 6 rats in each group. The effect of treatment was assessed by tumor growth delay （TGD）and radiosensitization enhancement cffector （EF）; the tumor tissues were collected and assessed for the detection of cyclooxygense-2 mRNA and prostaglandin E2 by RT-PCR and ELISA, and histopathological changes of transplanted mouse＇s important organs were observed. Results The time that the longest diameters of all tumors growing from 8.0mm to 12.0mm for the control group and the celecoxib group was（6.18＋0.72）d and（7.87_＋0.76）d, re- spectively ,while the time for the radiation group and celecoxib＋radiation group was （9.16＋0.89）d and （12.62＋1.28）d respectively. The growth of tumors was significan 05）and EF was 1.59; there was obvious differences in prostaglan tly different among these groups （P〈0. din E2 levels between the control group and other groups （P〈0.05 ）,while there was not obvious differences in prostaglandin E2 levels between the radiation group and celecoxib＋radiation group（P〉0.05）. Significant correlations were found between the growth delayed by celecoxib and the drop of prostaglandin E2 levels （r=0.807）; Analysis of variance showed that there was no significant difference in cyclooxygense-2 mRNA among these four groups （P 〉 0.05）. No significant toxic pathological changes of transplanted mouse＇s important organs were ob- served. Conclusion Our results suggest a coordinative repression between celecoxib and radiation in inhibiting human prostate carcinoma xenografts by the anti-tumor and rad