Salinomycin Pc - 3 For Prostate Cancer Cells And Stem Cells In Vitro Inhibition Mechanism Research

Objective: Observation the change of salinomycin effected on prostate cancer PC‐3cells proliferation in vitro and effected on the gene expression of cancer stem cells;Discuss the possible mechanisms of salinomycin effected on prostate cancer PC‐3cancer stem cells in vitro.Methods:1, Using10different concentrations of salinomycin(160、80、40ug/ml etc) effect on prostate cancer PC‐3cells, Paclitaxel for the control, using MTT to detect the half‐effect concentration (IC50μg/ml) and maximal inhibition rate (Imax) and draw the tumor cell growth curve;2, Randomly divided the prostate cancer PC‐3cells cultured in vitro into control group/experimental group/solvent group, choose the “CD133+、CD44+”cells as cancer stem cells, analysis the ratio of cancer stem cells in the three group by flow cytometry, and elect the cancer stem cells as cancer stem cells;3, Extract the total RNA of each group of tumor stem cells, Using chip screening to identify differential expression of2times、10times and the above genes,then were statistically analyzed.Results:(1), The IC50of salinomycin inhibits prostate cancer cell is9.18±6.66ug/ml, the Imax is99.35%;(2), Flow cytometry analysis results showed that the blank control group, cancer stem cell ratio average of0.83%, the experimental group cancer stem cell ratio average of0.46%, the difference of the two groups have statistical significance (p <0.05), while the solvent group of cancer stem cell ratio average of0.81%with the control group the difference did not have statistically significant (p>0.05);(3), The microarray results show that up‐regulated genes of1574, down1666,include26genes of experssion upregulation to more than10folds and21genes of downregulation to more than10folds,the FOLR1、CYP3A4、THBS1、MIER1、ATP2A3、LAMA4genes expression are connect with cancer stem cell apoptosis, growth, drug resistance and other biological characteristics.Conclusion:(1) Salinomycin can effectively inhibit proliforation of the prostate cancer PC‐3tumor cells in vitro;(2) Salinomycin can selective killing and inhibite the prostate cancer PC‐3cancer stem cells;(3) Salinomycin may be through upregulation of ATP2A3and down LAMA4gene expression to induce prostate cancer stem cells apoptosis,and then anti‐cancer stem cells.