Gao J, Jia W-D, Li J-S, Wang W, Xu G-L, Ma J-L, Ge Y-S, Yu J-H, Ren W-H, Liu W-B, Zhang C-H
Centre for the Study of Liver Cancer, and Department of Hepatic Surgery, Anhui Provincial Hospital, Anhui Medical University, Hefei, China.
J Int Med Res. 2010 Jul-Aug;38(4):1413-27. doi: 10.1177/147323001003800423.
This study was designed to investigate the in vivo growth inhibitory effects of celecoxib, a cyclo-oxygenase-2 inhibitor, and fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on the hepatocellular carcinoma (HCC) cell line, BEL-7402. Athymic nude mice implanted with BEL-7402 cells were given celecoxib and fluvastatin, either alone or in combination, and the effect of treatment on tumour growth was evaluated after 6 weeks. The combination of celecoxib and fluvastatin enhanced inhibition of tumour growth, induction of apoptosis, inhibition of tumour cell proliferation, and inhibition of tumour angiogenesis compared with either treatment alone. The combination of celecoxib and fluvastatin also increased levels of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1), decreased levels of p-Akt, myeloid cell leukaemia-1 (Mcl-1) and survivin protein, but had no effect on Akt protein levels in tumours. These results suggest that celecoxib combined with fluvastatin would be more efficacious for the treatment of HCC than either treatment alone and this combination of therapy warrants further research.
本研究旨在探讨环氧化酶-2抑制剂塞来昔布和3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂氟伐他汀对肝癌细胞系BEL-7402的体内生长抑制作用。将接种了BEL-7402细胞的无胸腺裸鼠单独或联合给予塞来昔布和氟伐他汀，6周后评估治疗对肿瘤生长的影响。与单独使用任一药物相比，塞来昔布和氟伐他汀联合使用增强了对肿瘤生长的抑制、诱导凋亡、抑制肿瘤细胞增殖以及抑制肿瘤血管生成。塞来昔布和氟伐他汀联合使用还提高了细胞周期蛋白依赖性激酶抑制剂p21（Waf1/Cip1）的水平，降低了p-Akt、髓样细胞白血病-1（Mcl-1）和生存素蛋白的水平，但对肿瘤中Akt蛋白水平无影响。这些结果表明，塞来昔布与氟伐他汀联合治疗肝癌比单独使用任一药物更有效，这种联合治疗值得进一步研究。
