Surfece Chemistry Induces Mitochondria-mediated Apoptosis Of Breast Cancer Cells Via PTEN/PI3K/AKT Signaling Pathway

Tumor cell behaviors can be significantly influenced by the functional groups with different hydrophilic-hydrophobic property in the extracellular matrix of cellular microenvironment.However,the molecular mechanisms of the correlation between cancer cells and functional groups remain unknown.Using surfaces modified with different chemical groups?CH₃,NH2,OH?,we investigated the role of these functional groups in modulating the apoptosis of MDA-MB-231 cells and its underlying mechanisms.Hydrophobic surfaces modified with CH₃ and NH2 suppressed cell proliferation via down-regulating percentage of cells in the S phase,accompanied by a sharp decline in cyclin D1 protein expression.Meanwhile,the numbers of apoptosis cells cultured on surfaces with CH₃ and NH2 significantly increased.Mitochondrial dysfunction,cytochrome c release,increased levels of Bax,cleaved caspase-3,PARP and reduced levels of the anti-apoptotic proteins Bcl-2 indicated that CH₃ and NH2 induce the activation of intrinsic apoptotic signaling.However,OH terminal functional group have no significant difference in cell proliferation and apoptosis compared with control.Therefore,we further investigate the molecular mechanism of hydrophobic surfaces induced mitochondria-mediated apoptosis of MDA-MB-231 cells by western blot and immunofluorescence.The cells that were poorly attached to substrates with CH₃ and NH2 showed down-regulated expression and activation of integrin ?1,which led to the activity of focal adhesion kinase?FAK?decreased.Thus the expression of RhoA,which is a downstream effector of FAK,as well as ROCK and PTEN in the cells that were poorly attached to substrates with CH₃ and NH2 were sharp increased.The resulting activated PTEN inhibited the activation of PI3 K and AKT,which is essential for cell proliferation.Pre-treating MDA-MB-231 cells with SF1670,a PTEN inhibitor,abolished the hydrophobic surfaces induced activation of intrinsic pathway.These results indicate that hydrophobic functional groups CH₃ and NH2 induce mitochondria-mediated apoptosis by suppressing the PTEN/PI3K/AKT,which might be potentially useful for designing novel cancer treatment strategies.