The Effect And Mechanism Of HEDGEHOG Singnaling Pathway On Invasion And Metastasis In Human Breast Cancer MDA-MB-231 Cells

Objective:To explore the effect and the possible mechanism of Hedg -ehog singaling pathway on invasiveness and metastasis in high invasive breast cancer MDA-MB-231 cells by MDA-MB-231 cells treated with Cyclopamine,a Hegehog singling pathway inhibitor.Methods: With breast cancer cells MDA-MB-231 as the research objec t, we used hedgehog pathway inhibitor Cyclopamine to treat MDA-MB-23 1cells, detected the proliferation by MTT , calculated the IC50 of 48 hours and detected the ability of invasion and metastasis in MDA-MB-231 cells by transwell chamber.Then we detected the expression of MMP-9 and MMP-2 section by gelatin zymography and detected the proteins expression of MMP-9 and uPA by Western blot. measured the mRNA levels of Gli1,c-jun,MMP-9 and uPA by reverse transcription-poly mera ge chain reaction(RT-PCR).Results:When MDA-MB-231 cells were treated with Cyclopamine , the proliferation of MDA-MB-231 cells were inhibited obviously(P<0.05), The intermediate concentration IC50 of Cyclopamine in MDA-MB-231 cells of 48 hours was 95.5μmol/L.When MDA-MB-231 cells were treated with 50μmol/L Cyclopamine for 48h hours, the invasion and migration were depressed(P<0.05). The expression of MMP-9 section was reduced(P<0.01).The expression level of P-c-jun,MMP-9 and uPA were decreased(P<0.01). The mRNA levels of Glil,c-jun,MMP-9 and uPA were reduced(P<0.01).Conclusion:The Hedgehog signaling pathway was activeted in MDA -MB-231 cells. The invasion and metastasis can be induced by activeted Hedgehog signaling pathway with up-regulation of c-jun MMP-9 and uPA leve1.