Growth Inhibiton of Human Breast Cancer Cell Line MDA-MB-231 by Rosiglitazone through Activation of PPARγ

OBJECTIVE To investigate the anti-proliferative effect ofrosiglitazone and its relationship to peroxisome proliferator-activated receptor γ(PPARγ)in human breast cancer cell lineMDA-MB-231 and evaluate the potential application value ofrosiglitazone for breast cancer therapy.METHODS The cytostatic effect of rosiglitazone on MDA-MB-231 cells was measured by the MTT assay.Cell-cyclekinetics was assessed by flow cytometry.Apoptotic cells weredetermined by the TUNEL assay.MDA-MB-231 cells weretreated with rosiglitazone or in combination with the PPARγantagonist GW9662 to investigate the effect of rosiglitazone on cellproliferation and its relationship to PPARγ.RESULTS The results showed that rosiglitazone could inhibitgrowth of MDA-MB-231 cells in a dose- and time-dependentmanner with an IC_(50)value of 5.2μmol/L at 24 h after the drugwas added into the culture.Cell cycle analysis showed that thepercentage of G_0/G_1 phase cells increased,S phase cells decreased,and cells were arrested in G_1 phase with increasing concentrationsof rosiglitazone.Detectable signs of apoptotic cell death caused byrosiglitazone occurred at a concentration of 100 μmol/L and theapoptotic rate was (18±3)%.PPARγ selective antagonist GW9662could partially reverse the inhibitory effect of rosiglitazone onproliferation of MDA-MB-231 cells.CONCLUSION It was concluded that rosiglitazone can inhibitgrowth of MDA-MB-231 cells via PPARγ activation and a highconcentration of rosiglitazone can also induce MDA-MB-231 cellapoptosis.These results suggest that PPARγ represents a putativemolecular target for chemopreventive therapy and rosiglitazonemay be effective in the treatment of breast cancer.

Biomimetic cell-adhesive ligand-functionalized peptide composite hydrogels maintain stemness of human amniotic mesenchymal stem cells

In vivo,stem cells reside in a three-dimensional(3D)extracellular microenvironment in which complicated biophysical and biochemical factors regulate their behaviors.Biomimicking of the stem cellmatrix interactions is an ideal approach for controlling the stem cell fate.This study investigates the effects of the incorporation of cell-adhesive ligands in 3D self-assembling peptide hydrogels to modulate stem cell survival,proliferation,maintenance of stemness,and osteogenic differentiation.The results show that the composite hydrogels were non-cytotoxic and effective for maintaining human amniotic mesenchymal stem cell(hAMSC)survival,proliferation and phenotypic characterization.The expression levels of pluripotent markers were also upregulated in the composite hydrogels.Under inductive media conditions,mineral deposition and mRNA expression levels of osteogenic genes of hAMSCs were enhanced.The increasing expression of integrin aand b-subunits for hAMSCs indicates that the ligandintegrin interactions may modulate the cell fate for hAMSCs in composite hydrogels.