塞来昔布对人三阴性乳腺癌裸鼠体内白细胞介素6和白细胞介素8水平的影响

Effects of Celecoxib on Interleukin-6 and Interleukin-8 Levels in Xenografted Nude Mice with Human Triple-negative Breast Cancer

目的探讨塞来昔布对人三阴性乳腺癌(TNBC)裸鼠体内白细胞介素6(IL-6)和IL-8水平的影响。方法人TNBC细胞MDA-MB-231接种于裸鼠背部皮下,建立人TNBC裸鼠移植瘤模型。随机分为对照组和塞来昔布低、中、高剂量组。42 d后观察裸鼠一般状况的变化、用药前后肿瘤生长情况及肿瘤质量变化;ELISA法检测各组裸鼠血清中IL-6和IL-8含量的变化;RT-PCR检测肿瘤组织中IL-6和IL-8 mRNA的变化;免疫组化法检测肿瘤组织中IL-6和IL-8蛋白表达的变化。结果塞来昔布各组肿瘤大小和瘤重较对照组均明显减小,差异均有统计学意义(P<0.05)。经塞来昔布治疗后,塞来昔布低、中、高剂量组裸鼠血清中IL-6和IL-8的含量明显降低,与对照组相比差异有统计学意义(P<0.05),肿瘤组织中IL-6和IL-8 mRNA及蛋白的表达均较对照组明显减少。结论塞来昔布可以抑制人TNBC裸鼠体内IL-6和IL-8的分泌及表达,进而影响肿瘤发展的进程。

Objective To evaluate the effects of celecoxib on interleukin-6（IL-6）and interleukin-8（IL-8）expression in established nude mice with human triple-negative breast cancer（TNBC）.Methods Human TNBC MDA-MB-231 cells were injected into BALB/c nude mice subcutaneously.The mice were randomly divided into 4 groups,including the control group and three celecoxib groups（receiving 25,50,100 mg.kg-1.d-1,respectively）.On the 42nd day,the tumor volume and tumor weight were measured and growth curves were analyzed.The serum level of IL-6 and IL-8 was detected by ELISA assay.The mRNAs and protein levels of IL-6 and IL-8 in tumor tissues were measured by RT-PCR and immunohistochemistry,respectively.Results Compared with control group,celecoxib at doses of 25,50 and 100 mg.kg-1.d-1 inhibited the tumor growth significantly（P 〈 0.05）.The serum levels of IL-6 and IL-8 were notably decreased in different celecoxib treatment groups.Meanwhile,the gene expression of IL-6 and IL-8 in tumor tissues was also markedly suppressed after celecoxib treatment.Conclusion Celecoxib can inhibit the secretion and expression of IL-6 and IL-8,thus preventing the progress of TNBC in vivo.