Secretory Leukocyte Peptidase Inhibitor (SLPI) Expression And Apoptosis Effect In Oral Leukoplakia And Oral Squamous Cell Carcinoma

Background: HNSCC is the sixth most common malignancy worldwide,1.66 million people diagnosed each year.Nearly half of them are oral squamous cell carcinoma.With the improvement of surgical technique and the progress of chemoradiotherapy,the survival rate of 5 years has increased,but it barely over 50%.OSCC is not a sudden formation,so early diagnosis and treatment are very important and it can greatly improve the patient’s survival rate and quality of life.Oral leukoplakia is considered as one of the most common precancerous lesions.Therefore,accurately determining the malignant transformation potential of oral leukoplakia and promptly blocking the development may be an important measure to prevent the occurrence of oral cancer.Objectives: Using non-invasively collected oral brush biopsies,our previous research indicated SLPI abundance in oral leukoplakia tissues is much lower than the expression in human normal oral epithelial tissues,with a more significant decrease in OSCC tissues.Based on above study,we initially investigate if SLPI is a potential predictive and diagnostic tool for the progress of oral carcinogenesis and research the biological effects and the regulation mechanism.Material and methods: The correlation between the abundance of SLPI protein and the different histological grades of oral leukoplakia was investigated by immunohistochemistry(IHC).Then,the biological effects of SLPI were researched by CCK-8,PI and Annexin V/PI apoptosis assay.The regulation mechanism was investigated by Caspase-Glo? 3/7 assay,NF-κB luciferase Reporter gene assay and real-time PCR.Results: It indicated that the level of SLPI is negatively correlated with the histological grades of OL,implying it may be a potential predictive tool for malignant transformation of OL(r=-0.4922,p<0.05).SLPI could promote apoptosis in Leuk1 and WSU-HN4 cell lines.Mechanistic studies indicated that SLPI may regulate cell apoptosis through NF-κB pathway.Conclusion: In conclusion,it’s the first time to find that the abundance of SLPI protein is negatively correlated with the grades of OL and it may have a potential prediction role for malignant transformation of OL.Our study revealed that SLPI protein has pro-apoptotic effect in OL and OSCC cell lines.It may be a potential therapeutic drug for OL and OSCC patients.However,more work is needed to be done to clarify the detailed mechanism.