【摘要】 目的探讨全反式维甲酸(ATRA)联用维生素D3(VD3)逆转肺癌细胞多药耐药、提高肺癌细胞化疗敏感性的机制。方法将ATRA、VD3联合作用于培养后的人肺癌原代细胞,观察肺癌原代细胞对顺铂化疗的敏感性及多药耐药相关蛋白(MRP)、肺耐药蛋白(LRP)的表达水平。结果人肺癌原代细胞MRP、LRP呈高表达;ATRA及VD3作用后肺腺癌原代细胞MRP、LRP表达量明显降低,肺鳞癌MRP、LRP的表达量无明显变化;顺铂化疗的敏感性提高。结论MRP、LRP在肺癌尤其非小细胞肺癌中高表达,可反映肿瘤细胞多药耐药性;ATRA或VD3可下调肺腺癌MRP、LRP基因的表达水平,提高肺腺癌的化疗敏感性;但对肺鳞癌MRP、LRP基因表达水平无明显影响;ATRA和VD3联用有协同作用。更多还原

【Abstract】 [Objective]To investigate the mechanism of ATRA and VD3 reversing multidrug resistance and the effect of ATRA and VD₃ on increasing chemosensitivity of lung cancer cells. [Methods] Primary cell culture, MTT colorimetric assay and RT-PCR were applied to observe the different effects induced by ATRA or VD₃ or ATRA and VD₃ on lung cancer cells. [Results]The frequency of expression of MRP, LRP was 54.7%, 58.5%, RT-PCR showed the significantly reduced expression of MRP and LRP in lung adenocarcinoma cells after ATRA and VD₃ treatment, but not in lung squamous carcinoma cells. The IC50 was significantly reduced after ATRA and VD₃ treatment. And the effect of ATRA and VD₃ were synergistic. [Conclusion] There is high expression of MRP and LRP in lung cancer cells, and which is the guiding clue of multidrug resistance. ATRA and VD₃ can increase the chemosensitivity by reduction of the expression of MRP, LRP in lung adenocarcinoma cells, but not obviously in lung squamous carcinoma cells. The effect of ATRA and VD₃ are synergistic.更多还原