DADS Ihibits The Invasion And Migration Of Breast Cancer Cells Via P38/TTP Pathway

OBJECTIVE To investigate the effect of disulfide(DADS) from the allicin allyl sulfide compounds on the invasion and migration of MCF-7 and MDA-MB-231 human breast cancer cell lines and the role of p38/TTP pathway in it so as to provide a new theoretical basis for the prevention and treatment of breast cancer.METHODS 1 MCF-7 and MDA-MB-231 cells were treated with different concentration(50?mol/L, 100?mol/L, 200?mol/L, 400?mol/L,600?mol/L) of DADS. Then, the tablet cloning experiments were performed to detect the cell colony formation. 2 The effects of DADS(100?mol/L, 200?mol/L, 400?mol/L) on the cell invasion and migration were determined with transwell and wound healing analysis. At the same time, the expression of uPA, MMP9, P-p38, p38 and TTP in MCF-7 and MDA-MB-231 cells were detected by western-blot. Further treated with 200?mol/L DADS for different time(6h, 12 h, 24 h, 48h), the tests mentioned above were used. 3 200?mol/L DADS and 24 h were chosen in the subsequent experiments. The effect of DADS on p38 pathway were tested using SB203580 or TGF-?1 to block or activate p38 signal. Transwell, wound healing assay and western blot were used.Furthermore, the protein expression of P-p38 was observed by immunofluorescence. 4 After TTP expression silenced by siRNA, the effects of DADS targeting TTP were observed.RESULTS 1 The tablet cloning experiments showed DADS could inhibit the colony formation of the two kinds of breast cancer cells. 2Transwell and wound healing assay were found that with the increasing dose of DADS, the invasion and migration of breast cancer cells were both dcreased. Western blot detection showed that DADS could up-regulate TTP and down-regulate the u PA, MMP9, P-p38 expression in a dose and time dependent. 3 SB203580 could increase the effects of DADS on inhibiting the invasion and migration of breast cancer cells and regulating the expression of TTP, uPA and MMP9 while TGF-?1 could activate the expression of P-p38 and reverse the effect of DADS mentioned above. 4 TTP siRNA could silence TTP expression and also reverse the effect of DADS mentioned above.CONCLUSIONS 1 DADS inhibits the invasion and migration of MCF-7 and MDA-MB-231 human breast cancer cells. 2 DADS could inhibit the invasion and migration of breast cancer cells and the expression of uPA and MMP9 by regulating p38/TTP pathway.