Primary Research Of The Inhibition Of PARP Inhibitor,Salin Omycin, Everolimus And Sunitinib On Breast Cancer BT-20 Stem Cells

BackgroundIn the theory of tumor stem cells, the stem cells of malignancy have the ability of self-renewal and multi-directional differentiation ,it’s the leading cause of tumor reappear and metastasis. The function of PARP is recognizing and repairing broken or fractured DNA chains.The mechanism of radiotherapy and chemotherapy is breaking the DNA of tumor cells, give rise to the death of cancer cells.PARP is an important cause of cancer cells to resistant to radiotherapy and chemotherapy, and it is becoming a new target to treat breast cancer.Salinomycin was verified that it could kill breast cancer stem cells.Everolimus is a inhibitor of mammalian target of rapamycin (mTOR),it is used as an antineoplastic drug or to inhibit the exclusive reaction of organ transplantation in clinic. Sunitinib is a multitargeted receptor tyrosine kinase inhibitor, it’s used to treat advanced renal cell carcinoma and gastrointestinal stromal tumors in clinic.ObjectiveAdd PAEP inhibitor (veliparib、olaparib、iniparib、)、salinomycin、everolimus and sunitinib to the medium of BT-20 cells, mark the ALDH1+ cells with ALDEFLUOR kit after 48 hours. Contrast the proportion of ALDH1+ cells in different teams to study the effect of all drugs on breast cancer stem cells.MethodsAdd drugs to the medium of BT-20 cells in different concentrations, 48 hours later, calculating IC50 of every drug in the MTT method. Select proper concentrations (10% inhibition ratio) of all drugs to BT-20 cells, labelling ALDH1+ cells of blank team and test team with ALDEFLUOR kit after 48 hours, detecting and contrasting the percentage of ALDH1+ cells of both groups in flow cytometryResultsThe IC50 of veliparib,olaparib,iniparib,salinomycin, everolimus and sunitinib were 32.23,38.65,35.12,8.21,5.73,7.85(mol/L).The ratio of ALDH1+ cells of blank team is (19.34±1.15)%, the experimental group is (10.87±2.24)%(salinomycin,1 μmol/L), (6.33±1.52)%(salinomycin,2μmol/L), (8.45±0.56)%(Olaparib, 10μm ol/L), (13.27±2.14)%(Veliparib, 10μmol/L), (6.83±2.67)%(Iniparib, 10μmol/ L), (9.82±1.74)%(everolimus, 1μmol/L), (7.87±2.52)%(sunitinib, 1μmol/L). Proportion of ALDH1+ cells of drug group is significant lower than blank groupConclusionPARP inhibitor (Veliparib、Olaparib、Iniparib)、salinomycin、everolimus、sunitini-b can significantly reduce the stem cells ratio in breast cancer cell line BT-20.