RNAi逆转淋巴瘤LRP和P-gp介导的多药耐药研究

Study of RNAi reversing P-gp and LRP mediated MDR in lymphoma

目的应用RNA干扰(RNA interference,RNAi)技术逆转淋巴瘤中P-糖蛋白(P-glycoprotein,P-gp)和肺耐药蛋白(lung resistance protein,LRP)介导的多药耐药(multidrug resistance,MDR)。方法采用细胞毒性试验、荧光定量PCR、Western blot等方法观测双靶向干扰载体对P-gp和LRP介导的MDR的逆转作用。结果采用干扰质粒转染耐药淋巴瘤细胞后,该细胞的耐药指数降低,外排米托蒽醌的能力降低,细胞中P-gp、LRP的mRNA和蛋白表达水平也显著降低,且差异均有统计学意义(P<0.05)。结论构建的双靶向干扰载体能在体外逆转淋巴瘤细胞中P-gp和LRP介导的非典型性多药耐药。

Objective To apply the RNAi technique to reverse P-glycoprotein（P-gp） and lung resistance protein（LRP） mediated multidrug resistance（MDR） in lymphoma.Methods To observe the reversal effect of double targeting interference vectors to P-gp and LRP mediated MDR by using cytotoxicity assay,efflux assays,fluorescence quantitative PCR,Western blot analysis,etc.Results After being transfected and infected by pSUPER-LRP and pAd-LRP,the multidrug resistance index of BJAB cell to mitoxantrone was decreased,the capacity of mitoxantrone efflux was weakened,the LRP mRNA and the LRP protein level was obviously decreased too.Conclusion Constructing double targeting interference vectors could almost completely reverse the LRP mediated atypical MDR in BJAB cell.