摘要
目的:研究高温43℃对多药耐药基因表达产物P-gp、MRP、LRP在蛋白水平上的影响及其生物学意义,更深入地了解热效应逆转耐药的机制.方法:采用免疫细胞化学染色法、RT-PCR以及Western blot方法,检测在不同温度和不同药物作用下,人胃癌耐药细胞株SGC7901/ADM和对照的人胃癌敏感细胞SGC7901株中,与人胃癌多药耐药相关的分子MDR1、P-gp、MRP、LRP在蛋白水平上的表达差异.结果:采用免疫细胞化学染色法检测人胃癌耐药株SGC7901/ADM细胞,发现高温43℃60 min处理可使P-gp蛋白表达下调率(down-regulated rate,DRR)31.78%(P=0.016),而MRP表达DRR为20.22%(P=0.037),差异有统计学意义,LRP未表达.采用Western blot法在SGC7901细胞中未检测出P-gp蛋白表达,而SGC7901/ADM细胞中P-gp高表达;在ADM和CDDP处理组细胞中,高温43℃时P-gp的表达量较37℃时DRR分别为45.65%(P=0.007)、17.95%(P=0.021),差异有显著学意义;TAX处理组DRR为11.90%,差异无显著学意义(P=0.065).结论:高温43℃的短期处理对人胃癌SGC7901/ADM细胞中P-gp和MRP多药耐药蛋白的表达有一定的抑制作用,可能是逆转耐药的机制之一.
AIM： To observe the effect of hyperthermia at 43 ℃ on the expression of multidrug resistance-related markers,MDR1,MRP,and LRP in adriamycin（ADM）-resistant human gastric cancer cell line SGC-7901/ADM,and to determine the possible mechanisms underlying the reversal effect of hyperthermia on multidrug resistance.METHODS： The expression of multidrug resistance molecules MDR1,P-gp,MRP,and LRP in SGC7901/ADM cells treated by hyperthermia at 43°C was assayed by immunocytochemistry,Western blot,and RT-PCR.RESULTS： The expression of P-gp and MRP was reduced by 31.78%（P = 0.016） and 20.22%（P = 0.037）,respectively,in SGC7901/ADM cells exposed to high temperature at 43 ℃ for 60 min,but LRP expression cannot be measured by immunocytochemistry.P-gp expression could not be detected in ADM-sensitive human gastric cancer cell line SGC7901 by Western blot;however,high expression of P-gp was detected in SGC7901/ADM cells.The expression of P-gp could be decreased by high temperature at 43 ℃ in all drug groups,and the expression of P-gp was reduced by 5.65%（P = 0.007）,17.95%（P = 0.021）,11.90%（P = 0.065） in ADM,CDDP and TAX groups,respectively.CONCLUSION： High temperature at 43 ℃ could partially inhibit the expression of multidrug resistance-related molecules P-gp and MRP in ADM-resistant human gastric cancer cell line SGC7901/ADM.
出处
《世界华人消化杂志》
CAS
北大核心
2012年第22期2075-2080,共6页
World Chinese Journal of Digestology
