塞来昔布与耐多药转运蛋白的相互作用提高了丝裂霉素C的活性在膀胱癌细胞系。
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Pagliarulo V,安科纳P,你M, Colabufo NA, Contino M, Cormio L, Azzariti, Pagliarulo
塞来昔布与耐多药转运蛋白的相互作用提高了丝裂霉素C的活性在膀胱癌细胞系。
摩尔癌症。2013年5月24日,47。doi: 10.1186 / 1476-4598-12-47。
- PubMed ID
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23705854 (在PubMed]
- 文摘
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背景:开发出相应的体外模型,了解如果塞来昔布可能协同丝裂霉素C (MMC),常用non-muscle浸润性膀胱癌复发的预防,并最终阐明如果交互涉及到多重耐药的机制(MDR)转运蛋白。方法:UMUC-3,非cox - 2表达膀胱癌细胞系,UMUC-3-CX, cox - 2 overexpressing转染子,以及5637年,cox - 2 overexpressing细胞系,和5637 si-cx,非cox - 2表达沉默5637细胞系,被用于本研究。cox - 2的表达和耐多药泵(P-gp MDR-1和BCRP)探讨了通过免疫印迹。塞来昔布和MMC的anti-proliferative效果与MTT测试进行了研究。三个生物渗透化验(药物运输实验、衬底运输车抑制和细胞ATP耗竭)相结合,研究了耐多药转运蛋白之间的相互作用和塞来昔布。最后,塞来昔布的能力恢复MMC细胞积累进行了研究。结果:塞来昔布的anti-proliferative效果和MMC进行合并施打,在UMUC-3 UMUC-3-CX, 5637年和5637年si-cx细胞。当单独管理,MMC在UMUC-3八大的影响。然而,合并施打1妈妈,5妈妈,和10个妈妈塞来昔布和MMC引起了2,3重UMUC-3-CX细胞细胞毒性增加。MMC细胞毒性并不影响塞来昔布合并施打要么在5637年或5637年si-cx细胞。 As a result of all finding from the permeability experiments, celecoxib was classified as P-gp unambiguous substrate: celecoxib is transported by MDR pumps and interferes with the efflux of MMC. Importantly, among all transporters, BCRP was only overexpressed in UMUC-3-CX cells, but not in 5637 and 5637si-CX. CONCLUSIONS: The UMUC-3-CX cell line resembles a more aggressive phenotype with a lower response to MMC compared to the wt counterpart. However, the administration of celecoxib in combination to MMC causes a significant and dose dependent gain of the anti-proliferative activity. This finding may be the result of a direct interaction between celecoxib and MDR transporters. Indeed, BCRP is overexpressed in UMUC-3-CX, but not in UMUC-3, 5637, and 5637si-CX, in which celecoxib is ineffective.