In Vitro Study Of Tyrosine Kinase Receptor Inhibitor Combined With Cisplatin On Head And Neck Squamous Cell Carcinoma

Objective:Study to Capmatinib which is the combination of type IB hepatocyte growth factor receptor inhibitor and Cisplatin in the treatment of head and neck squamous cell carcinoma in the vitro.Methods:The expression of Met gene was correlated with the prognosis of head and neck squamous cell carcinoma(HNSCC)by processing the data of head and neck squamous cell carcinoma in(TCGA)database.The cytotoxicity of Capmatinib and Cisplatin on HN30 head and neck squamous cell carcinoma cells was studied by Cell Counting Kit-8(CCK-8)method.The survival rate of HN30 head and neck squamous cell carcinoma cells treated with Capmatinib combined with Cisplatin was detected.Detection of western blot after combined treatment The changes of DNA damage ability and downstream PI3K/Akt signal pathway of c-Met were detected by flow cytometry,and the changes of apoptosis ability were detected by flow cytometry.Results:Cisplatin’s IC50=6.14 μmol/mL;Capmatinib’s IC50=1.597μmol/L;Capmatinib was obtained from HN30 head and neck squamous cell carcinoma cells.HN30 head and neck squamous cell carcinoma cell line was co-cultured with 6 μmol/mL Capmatinib and 1.6μmol/L Cisplatin for 24 h.The survival rate of HN30 head and neck squamous cell carcinoma cells was(56.27±1.36)%in 24 h group,and(97.21±2.59)%in control group of HN30 head and neck squamous cell carcinoma cells.There was significant difference between the two groups(P<0 05),and the degree of DNA damage in the cells was significantly higher than that in the control group(P<0 05),and there was a significant difference between the two groups(P<0.05).Both met-KD cells and Capmatinib-inhibited cells could regulate the expression of PI3K/Aktl,p-c-Met,p-Aktl by inhibiting the expression of PI3K/Aktl,p-c-Met,p-Aktl.When HN30 head and neck squamous cell carcinoma cells were treated with Capmatinib and Cisplatin,the results were compared with those treated with other drugs alone.Compared with the control group,there was a decrease in both.The apoptosis of HN30 cells treated with Capmatinib and Cisplatin was detected by flow cytometry.The percentage of apoptosis of HN30 cells in blank control group was(3.75±1.43)%,that in Capmatinib group was(16.72±2.74)%,respectively.The percentage of apoptosis was(35.43±8.51)%in Cisplatin group and(57.31±10.83)%in combined group.Conclusion:The expression of Met gene is correlated with survival rate in head and neck squamous cell carcinoma.The expression of Met gene was negatively correlated with the overall survival rate of the patients.Capmatinib,a small molecular inhibitor of Met,could regulate downstream PI3K/AKT signaling pathway by specifically inhibiting the expression of c-Met in HN30 head and neck squamous cell carcinoma cells.The expression of p-PI3k and p-AKT decreased,and Capmatinib could regulate downstream PI3K/AKT signaling by inhibiting phosphorylation of c-Met protein.Met small molecule inhibitor Capmatinib can inhibit the expression of y-H2AX by inhibiting the phosphorylation of c-Met protein,which can inhibit the proliferation of HN30 head and neck squamous cell carcinoma cells.To regulate the DNA self-repair mechanism of HN30 head and neck squamous cell carcinoma cells.Capmatinib combined with Cisplatin can promote the apoptosis of HN30 head and neck squamous cell carcinoma cells after treatment,and the apoptosis of HN30 head and neck squamous cell carcinoma cells is promoted by Capmatinib in combination with Cisplatin.Capmatinib may be a potential target drug for head and neck squamous cell carcinoma in the future,and it is expected that Capmatinib may be a potential target drug for head and neck squamous cell carcinoma in the future.It provides a new prospect for the adjuvant therapy of head and neck squamous cell carcinoma.Figure[13]table[4]reference[73]...