目的比较研究不同温度的热疗对人乳腺癌株MCF-7细胞侵袭转移能力的影响及其相关分子机制。方法水浴热疗43、45和47℃3组MCF-7细胞各30min,37℃为对照组。采用免疫组织化学染色法检测 MCF-7细胞转化生长因子-β1(TGF—β1)、血管内皮生长因子(VEGF)蛋白的表达;明胶酶谱法检测细胞上清液中基质金属蛋白酶(MMP)-2、MMP-9的分泌及活性。结果热疗对MMP-2、MMP-9的释放和激活均有明显的抑制作用(P〈0.05);且对MMP-2活性的抑制作用有明显的温度依赖性,随加热温度增加,抑制作用越明显(P〈0.05)。各热疗组TGF—β1和VEGF的表达均较对照组显著下降(P〈0.05),但不同温度热疗组之间差异无统计学意义(P〉0.05);结论43、45、47℃热疗均可下调MCF-7细胞中TGF—β1、VEGF的蛋白表达及抑制MMP-2、MMP-9的分泌和活性,从而抑制人乳腺癌细胞侵袭转移能力。
Objective To study the effects of hyperthermia with different temperature on inhibiting invasiveness and metastasis of human breast adenocarcinoma cells(MCF-7) and its possible mechanism. Methods MCF-7 was treated by heating with different temperatures(43 ℃,45 ℃ and 47 ℃ )for 30 minites and 37 ℃ as control. Expression of matrix metalloproteinase (MMP) - 2, MMP- 9, vascular endothelial growth factor ( VEGF), transforming growthfactor(TGF)- β1 of MCF-7 after different heating temperatures treatment was examined by immuno-cytochemical technique;The effect of hyperthermia on MMP-2, MMP-9 expression, activity were also studied by gelatin zymograpbic assays. Results Comparing with 37 ℃ group, byperthermia with 43 ℃ ,45 ℃ and 47℃ also decreased MMP-2,MMP-9 enzymatic activifiesl which is temperature-dependant( P 〈 0.05). The VEGF,TGF-131 protein expression in 43 ℃ ,45 ℃ and 47 ℃ groups decreased significantly( P 〈0. 05), but there is no differeme between heating groups ( P 〉 0. 05). Conclusion Hyperthermia as potential treat- ment inhibits invasion by a process involved in muhiple regulatory molecules in MCF-7.