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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PGE2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PGE2含量的下降呈正相关(r=0.807);4组移植瘤组织中COX-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。
Objective To study the antitumor effect and radiosensitizing effect of selective cyclooxygenase-2 (COX-2) inhibitor celecoxib on prostate cancer and to explore the mechanism of its synergistic inhibitory effect. Methods Human prostate cancer xenografts model was established by using prostate cancer PC-3 cells. The nude mice bearing tumor were randomly divided into 4 groups: control group, celecoxib group, radiotherapy group and celecoxib combined radiotherapy group, with 6 in each group. The tumor growth delay time (TGD) and the sensitization coefficient (EF) of the tumor were observed. The content of prostaglandin E2 (PGE2) was determined by radioimmunoassay (ELISA) and the expression of PGE2 was detected by reverse transcriptase polymerase chain reaction The expression of COX-2mRNA in the xenografted tumor tissue was observed. The pathological changes of the major organs in the tumor-bearing mice were also observed. Results The time required for the maximum diameter of the tumor to grow from 8.0 mm to 12.0 mm in the control and celecoxib groups was (6.18 ± 0.72) days and (7.87 ± 0.76) days, respectively, while the radiotherapy group and the celecoxib combined with radiotherapy group were (9.16 ± 0.89) d and (12.62 ± 1.28) d, respectively. The difference between the two groups was statistically significant (P <0.05) and EF was 1.59. There was significant difference in PGE2 content between the control group and the other three groups (P <0.05) , While there was no significant difference between the radiotherapy group and the celecoxib radiotherapy group (P> 0.05). The growth delay induced by celecoxib was positively correlated with the decrease of PGE2 level (r = 0.807). The COX-2 mRNA There was no significant difference in expression level between the two groups (P> 0.05). No significant pathological changes were observed in the vital organs of tumor bearing mice. Conclusion Celecoxib combined with radiotherapy in the treatment of human prostate cancer subcutaneously transplanted tumor in nude mice has anti-tumor effect and radiosensitization effect, which can exert a synergistic inhibitory effect and is safe and effective in a certain range, which is provided for the future research and clinical treatment of prostate cancer A certain idea.