塞来昔布联合顺铂对人舌鳞癌Tca8113细胞移植瘤的生长抑制作用

Inhibitory effect of celecoxib combined with cisplatin on xenografts of Tca8113 cells in vivo

目的:通过动物实验观察COX-2抑制剂塞莱昔布与顺铂联合应用后对人舌鳞癌Tca8113细胞移植瘤的生长抑制作用。方法:将Tca8113细胞接种于裸鼠皮下,分别给予塞来昔布、顺铂及两者联合应用,35d后处死裸鼠,测移植瘤质量,计算抑瘤率,光镜及电镜观察移植瘤组织学变化,免疫组化染色观察COX-2蛋白的表达,RT-PCR检测COX-2mRNA表达。结果:COX-2抑制剂塞来昔布除抑制Tca8113细胞移植瘤生长及COX-2蛋白的表达外,还显著增强顺铂对移植瘤的生长抑制作用。塞来昔布组、顺铂组及塞来昔布+顺铂组的抑瘤率分别为15.63%、37.50%和82.81%,与对照组相比差异有统计学意义,P<0.01;塞来昔布+顺铂组与塞来昔布及顺铂单独用药组相比,其抑制移植瘤生长差异有统计学意义,P<0.01;塞来昔布对Tca8113细胞COX-2mRNA表达的抑制作用较弱,与对照组相比差异无统计学意义,P=0.073。结论:塞来昔布除了可以抑制裸鼠移植瘤生长外,还可以增强顺铂对Tca8113细胞裸鼠移植瘤生长抑制作用,其作用机制可能与抑制COX-2蛋白的表达有关,为进一步探索抑制COX-2酶的活性与防治头颈肿瘤的作用机制方面,提供了有益的参考。

OBJECTIVE：To investigate the inhibitory role of celecoxib combined with cisplatin（DDP） on human tongue squamous cell carcinoma cell line Tca8113 in vivo.METHODS：Nude mice bearing xenografts were treated with as follows：celecoxib,DDP,and celecoxib plus DDP and control.At 35 d after administration,the nude mice were sacrificed and tumor masses were dissected and weighed for calculating tumor inhibition rates.The histological and electron microscopic analyses were used to observe the nude mouse tumor tissues.The immunohistochemistry staining was employed for COX-2 protein expression and fluorescent quantitive real-time RT-PCR was used to detect COX-2 mRNA expression.RESULTS：COX-2 proteins were strongly expressed in the control group while their expressions were significantly decreased in the groups of celecoxib and celecoxib plus DDP.COX-2 inhibitor celecoxib could enhance the inhibition of DDP on the growth of Tca8113 xenograft.The inhibition rates in the celecoxib group,DDP group and celecoxib plus DDP group were 15.63%,37.50% and 82.81%,respectively,which were statistically significant compared with the control group （P〈0.01）.Compared with celecoxib and DDP groups,the inhibitory effect of celecoxib plus DDP was statistically significant （P〈0.01）.The results of RT-PCR showed that celecoxib was less active in inhibiting the expression of COX-2 mRNA （P=0.073）.CONCLUSIONS：COX-2 inhibitor celecoxib is capable of enhancing the killing effect of DDP on Tca8113 cells.When co-administered with DDP,the inhibitory effect of DDP on the growth of xenografts in nude mice is significantly enhanced.