The Study Of The Effect And Mechanism Of Chlorpromazine And Trifluoperazine On The Lung Cancer Cells

Cancer,one of the most lethal diseases,is serious harmful to people’s lives.It is very necessary to find out the effective prevention and treatment for the incidence increased year by year.Lung cancer is one of the most popular malignant tumors and has the highest fatality rate of the malignant tumors.Chlorpromazine and trifluoperazine,treatment of psychiatric,has attracted researchers’ attention.Chlorpromazine and trifluoperazine belong phenothiazine anti-psychotic drugs.As a major discovery in the treatment of psychosis,chlorpromazine and trifluoperazine winded clinical for controlling schizophrenia or other mental illness,agitation,nervous and so on.Chlorpromazine and trifluoperazine possess cytotoxic activity against several tumor cells in addition to their treatment of psychosis,for which the possibility of their use as anticancer agents is currently investigated.In the study of chlorpromazine,trifluoperazine anti-small cell lung cancer activity and its mechanism.MTT assay show that the proliferation of NCI-H446 cells was inhibited by chlorpromazine and trifluoperazine in a concentration-dependent manner,with an IC50 value of 30.91μM and 25.02μM.Wound Healing and Transwell invasion assay respectively show that chlorpromazine and trifluoperazine have good ability to inhibit cancer cell migration and invasion.We detected the change of E-cadherin and N-cadherin,molecular markers of epithelial mesenchymal transformation by immunofluorescence and high-content screening,we found that chlorpromazine and trifluoperazine increased E-cadherin levels and decreased N-cadherin protein expression.Luciferase reporter gene assay was tested for transcription factors associated with cancer cells,such as Twistl,Twist2,Snail1,Snail2,NANOG,SOX2,KLF4,POU5F1,VEGFR1,VEGFR2.We found that chlorpromazine and trifluoperazine have significant function of regulating expression of transcription factors,chlorpromazine and trifluoperazine were verified anti-tumor mechanisms at the molecular level.Moreover,tube formation assay show that after dosing NCI-H446 cells forming vascular pipeline capacity decreased significantly,and in a concentration dependent manner,which was consistent with the dual luciferase reporter gene assay showed,chlorpromazine and trifluoperazine could significantly reduce the expression of VEGFR1 and VEGFR2.At the end of the experiment,we explored the chlorpromazine and trifluoperazine antitumor active site preliminary.This study found multiple experiment proved that chlorpromazine and trifluoperazine reverses epithelial-to-mesenchymal transition and suppresses the proliferation and metastasis of lung cancer cells.We further development of chlorpromazine and trifluoperazine antitumor "new use",to provide cheap,safe and lower side effects of anti-metastasis drugs for clinical cancer patients.