1，25-（OH）2 VitD3对人胰腺癌细胞侵袭迁移能力及 MMP-2、9、14表达的影响

摘要

目的：观察1，25-二羟基维生素 D3[1，25-（OH）2 VitD3]对人胰腺癌 PANC-1细胞侵袭迁移能力的影响，以及基质金属蛋白酶（MMP）-2、9、14的表达变化。方法将不同浓度（0、25、50、75、100μmol／L）的1，25-（OH）2 VitD3作用于 PANC-1细胞，干预24 h 时分别用 Transwell 细胞侵袭、迁移实验观察细胞的侵袭和迁移能力，干预48 h 时用 Western blot 法检测细胞 MMP-2、9、14蛋白。结果0、25、50、75、100μmol／L 的1，25-（OH）2 VitD3干预 PANC-1细胞24 h 时，侵袭细胞数分别为（46．20±0．84）、（30．80±2．28）、（18．80±1．64）、（13．20±2．39）、（5．20±1．30）个／HP，迁移细胞数分别为（66．03±1．25）、（55．82±1．65）、（41．43±1．51）、（19．86±1．45）、（10．23±1．95）个／HP；随着1，25-（OH）2 VitD3浓度增加侵袭及迁移细胞数逐渐减少，差异有统计学意义（P 均＜0．05）。1，25-（OH）2 VitD3干预 PANC-1细胞48 h 后，随着1，25-（OH）2 VitD3浓度增加 PANC-1细胞 MMP-2、9、14蛋白相对表达量逐渐减少，差异有统计学意义（P 均＜0．05）。结论1，25-（OH）2 VitD3可通过下调 MMP-2、9、14蛋白的表达，从而抑制胰腺癌 PANC-1细胞的侵袭与迁移。%Objective To investigate the effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ]on invasive and migra-tory abilities of human pancreatic cancer cell line PANC-1 and the changes in the expression of matrix metalloproteinases (MMP)-2,9 and 14.Methods The routinely cultured human pancreatic cancer cell line PANC-1 in vitro was treated with different concentrations of 1,25(OH)2 D3 (0,25,50,75 and 100 μmol/L).After 24 hours,the abilities of migra-tion and invasion in vitro in each group were detected by Transwell migration and invasion assays.After 48 hours,the pro-tein expression of MMP-2,9 and 14 in each group was measured by Western blotting.Results After intervention for 24 h with different concentrations of 1,25(OH)2 D3 (0,25,50,75 and 100 μmol/L),every field′s invasive cells in each group were (46.20 ±0.84),(30.80 ±2.28),(18.80 ±1.64),(13.20 ±2.39)and (5.20 ±1.30)/HP;and the migratory cells in each group were (66.03 ±1.25),(55.82 ±1.65),(41.43 ±1.51),(19.86 ±1.45)and (10.23 ±1.95)/HP,respectively.The migratory and invasive cells were decreased with the increase of concentration,and the difference was statistically significant (all P <0.05).After intervention for 48 h with different concentrations of 1,25 (OH)2 D3 , MMP-2,9 and 14 protein expression showed a declining trend with the increase of concentration,and the difference was statistically significant (all P <0.05).Conclusion 1,25(OH)2 D3 can inhibit the invasion and migration of PANC-1 cells through down-regulating the expression of MMP-2,9 and 14.