Zhao Gang,Zheng Taihao,Huang Xiu,Wu Chunrong,Li Meng,Li Ming.Role of microRNA-451 in reversion of multidrug resistance mediated by MDR1/P-gp pathway in colorectal carcinoma[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(02):155-160.
Zhao Gang,Zheng Taihao,Huang Xiu,Wu Chunrong,Li Meng,Li Ming.Role of microRNA-451 in reversion of multidrug resistance mediated by MDR1/P-gp pathway in colorectal carcinoma[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(02):155-160.DOI:
Role of microRNA-451 in reversion of multidrug resistance mediated by MDR1/P-gp pathway in colorectal carcinoma
Objective To investigate the expression of microRNA-451 in colorectal cancer (CRC) tissue and cell lines
and explore its role in multidrug resistance mediated by multidrug resistance gene 1 (MDR1)/P-glycoprotein (P-gp) pathway. Methods The expression of microRNA-451 and P-gp in 68 cases of CRC and matched non-tumor adjacent tissues was detected by RT-qPCR and Western blotting
and
the correlation was analyzed. The expression of microRNA-451 in CRC cells (HCT116 and LoVo) and corresponding drug-resistant cells [HCT116/oxaliplation (L-OHP) and LoVo/adriamycin (Adr)
]
was detected by RT-qPCR. The drug-resistant cells were transfected with microRNA-451 mimics and NC RNAs using Lipofectamine 2000
and then the expression of MDR1 and P-gp was measured by RT-qPCR and Western blotting. The proliferation of the transfected resistant cells treated with different concentrations of L-OHP or Adr was detected by MTT assay
and the IC
50
values were calculated. Flow cytometry was used to analyze the apoptotic rate of the transfected resistant cells treated with the same concentration of L-OHP or Adr. Results Compared with the non-tumor adjacent tissues
microRNA-451 exhibited lower expression level in CRC tissues
and its down-regulation was associated with P-gp positive expression (r=-0.404
P=0.002). The microRNA-451 levels were significantly lower in HCT-116/L-OHP cells and LoVo/Adr cells than in their parental cells (P0.01). The expression of MDR1 mRNA and P-gp was decreased in the microRNA-451 mimic transfection group as compared with the NC RNA transfection group
moreover
the IC
50
and apoptotic rate had significant differences between the 2 groups (P0.05). Conclusion MicroRNA-451 contributes to multidrug resistance through modulating the expression of MDR1/P-gp in colorectal carcinoma
and its overexpression can partly reverse the multidrug resistance.
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