The Effect Of Montelukast Soudium On The Androgen Independent Prostate Cancer Cells Proliferation And Apoptosis

Objective:The research aimed to explore the mechanism of Montelukast Sodium on the proliferation and apoptosis of androgen independent prostate cancer cells. Additionally, This study can throw light to clinical treatment of androgen independent prostate cancer with new theory.Methods:We used PC3 and DU145 which were the both important cells denoted androgen independent prostate cancer as our research cells. The experiments designed as follows:drug group and control group. The drug group was treated with Montelukast Sodium, and the control group without treating drags. Drug group and control group were respectively processed at different concentrations (3μg/ml,1.5μg/ml) and different drug effcet time (Oh,24h,48h) to explore the effects and mechanisms of the Montelukast Sodium on the proliferation and apoptosis of DU145 and PC3. The details experiment methods are in the follows:(1) The CCK8 assay was used to investicate the growth activity, proliferation, cytotoxicity and growth inhibition of DU145 and PC3 cells, after treatng with MSH.(2) Ordinary optical inverted microscope was used to observe the morphological changes of the DU145 and PC3 cells treating with MSH under an inverted light microscope.(3) Cell wound scratch assay was used to detect the inhibiting effect on the migration of DU145 and PC3 cells after treating with MSH.(4) SEM and TEM was used to further confirm the morphological changes of the DU145 and PC3 cells apoptosis after treating with MSH.(5) Real-Time PCR was used to detect the expression of apoptosis related genes bcl2 and bax, and the reference gene was GAPDH.Results:(1) The CCK8 results demonstrated that Montelukast Sodium could obviously inhibit the PC3 and DU145 cells proliferation and cytotoxicity. Both IC50 values were 3μg/ml from the growth curves.(2) Under the ordinary inverted optical microscope, there were obvious morphological differences between the control group and drug groups. The growth of controls was normal, but the drug groups were obvious apoptosis.(3) The cell wound scratch assay confirmed that the growth and migration abilities of DU145 andPC3 cells were significantly inhibited. The cells of control group appeared obviously migrated after 24h, and migrated completely after 48h healing. However, the treating with Montelukast Sodium showed no obvious migration and cells apoptosis after 24h. Additionally, a large number of cells appeared apoptosis, and no migration after 48h.(4) After processing DU145 and PC3 cells with Montelukast Sodium, the results of SEM and TEM demonstrated that the morphological structure of PC3 and DU145 appeared obvious apoptosis phenomenon.(5) The results of real time PCR showed that Montelukast Sodium could induced significant changing on mRNA expression of bcl2, bax after treating DU145 and PC3 cells with Montelukast Sodium. Both bcl2 and bax were up-regulated expression of mRNA in PC3 cells. However,in DU145 cells, the bcl2 were down-regulated expression of mRNA; the bax were up-regulated expression at 24h and down-regulated expression at 48h.Conclusion:We further confirm that Montelukast Sodium can obviously affect the proliferation and apoptosis of DU145 and PC3. This study can give important theory for the treating of androgen independtent prostate cancer, and throw light on future further research.