Investigation About The Effect Of Sorafenib On HaCaT Cells Based On MAPK Pathway

BacKgroundPsoriasis is a common,recurrent,chronic.inflammatory and systemic disease in dermatology.affecting 2%?3%of the world population[1].This disease has a high recurrence rate and a long course,which has a serious impact on the physical and mental health of the patients.The treatment of psoriasis is difficult and has been one of the research focuses of clinical worKers.Although there are many ways to treat psoriasis and new drugs are emerging,they still cannot meet the clinical needs.Sorafenib is a Kind of multi-Kinase inhibitor,which is mainly used in the treatment of tumor diseases such as liver cancer and Kidney cancer.lt can act on the targets such as RAF Kinase,platelet derived growth factor(PDGF),vegfr-1,vegfr-2,vegfr-3,platelet derived growth factor receptor(PDGFR)-?and c-Kit,and has significant inhibitory and regulatory effects on euKaryotic cell proliferation and differentiation by influencing MAPK pathway.Abnormal Keratinocytes proliferation and differentiation is an important mechanism of psoriasis and an important basis for the treatment of psoriasis.Studies have shown relief of psoriasis symptoms in cancer patients with sorafenib,suggesting the potential value of sorafenib in the treatment of psoriasis,but there have also been reports of exacerbations of symptoms.In view of this,this study will investigate the possible role of sorafenib in psoriasis based on Keratinocy-tes proliferation and differentiation.ObjectiveChanges in the proliferation metabolism and related gene expression of HaCaT cells treated with sorafenib were determined to understand the effect of sorafenib on Keratinocytes.MethodsHaCaT cells were used as cell models for psoriasis.The effects of different concentrations of sorafenib on the proliferation phenotype of Hacat cells were observed,and the inhibitory effect of sorafenib on the activity of Hacat cells was determined by MTT assay(full writing).Rt-pcr was used to detect the effect of sorafenib on the expression of EGR1?KRT1?KRT6A?KRT10?TGM1 which is related to the proliferation and differentiation of HaCaT cells.ResultsIt was found that sorafenib had a dose-dependent effect on the viability of HaCaT cells.and the IC50 of sorafenib was 9.549 ?m/ml.According to the RT-PCR results,the expression abundance of EGR1 in sorafenib group was 0.337 times that of the control group in HaCaT cells.The expression abundance of EGR1 was 0.337 times that of the control group.The expression abundance of KRT1 was 7.064 times that of the control group.The expression abundance of KRT6A was 20.884 times that of the control group.The expression abundance of KRT10 was 9.085 times that of the control group.The expression abundance TGM1 was 0.474 times that of the control group.ConclusionSorafenib directly inhibited the proliferation of Hacat cells and affected the gene expression of proliferation-related proteins.It is suggested that it has potential therapeutic significance for psoriasis.