PI-103对人黑色素瘤A375细胞迁移和侵袭能力的影响及其机制研究

摘要

Objective To investigate the effects of PI-103 on the migratory and invasive abilities of human melanoma A375 cells in vitro and its mechanism. Methods The effects of PI-103 with different concentration on the proliferation of A375 cells were detected by MTT assay. The effects of PI-103 at 0.1, 0.2 μmol/L concentration on the migratory and invasive abilities of A375 cells were detected by transwell chamber assay. The expressions of MMP-2 and MMP-9 in A375 cells were determined by Western Blot. Results The inhibition effects on the proliferation of A375 cells treat-ed with PI-103 at 0.1, 0.2μmol/L concentration were not significant (P>0.05). The proliferation of A375 cells treated with PI-103 at the concentration higher than 0.4μmol/L was significantly inhibited (P<0.05). The numbers of trans-membrane cells in the migration and invasion experiment treated with PI-103 at 0.1 μmol/L concentration were (91.73±13.80), (63.67±8.54) respectively, which were significantly decreased compared with control group (P< 0.05). The numbers of transmembrane cells in the migration and invasion experiment treated with PI-103 at 0.2 μmol/L con-centration were (64.07±9.22), (34.80±7.89) respectively, which were significantly decreased compared with control group (P< 0.05). The expressions of MMP-2 and MMP-9 in A375 cells treated with PI-103 at 0.1, 0.2 μmol/L con-centration were significantly decreased compared with control group (P< 0.05). Conclusion PI-103 can inhibit the mi-gration and invasion of A375 cells by down-regulation of the expressions of MMP-2 and MMP-9, which provide the experimental basis for the prevention of melanoma metastasis.%目的：观察PI-103在体外对人黑色素瘤A375细胞迁移和侵袭能力的影响,并探讨可能的作用机制。方法应用MTT法检测不同浓度PI-103对A375细胞增殖的影响,Transwell小室实验检测0.1、0.2μmol/L PI-103对A375细胞迁移能力和侵袭能力的影响,Western Blot法测定细胞基质金属蛋白酶(MMP)-2、MMP-9的表达。结果0.1、0.2μmol/L PI-103对A375细胞增殖的抑制作用不明显(P跃0.05)；在浓度高于0.4μmol/L时,PI-103能够明显抑制A375细胞的增殖(P<0.05)。0.1μmol/L PI-103作用后,迁移实验和运动实验穿膜细胞数分别为(91.73±13.80)、(63.67±8.54),与对照组比较明显减少,差异有统计学意义(P<0.05)；0.2μmol/L PI-103作用后,迁移实验和运动实验穿膜细胞数分别为(64.07±9.22)、(34.80±7.89),与对照组比较明显减少,差异有统计学意义(P<0.05)。0.1、0.2μmol/L PI-103作用后,A375细胞MMP-2、MMP-9蛋白表达明显低于对照组,差异有统计学意义(P<0.05)。结论 PI-103可通过下调MMP-2、MMP-9的表达抑制A375细胞迁移和侵袭,为其应用于抗恶性黑素瘤转移治疗提供了实验依据。