| Objective: Primary liver cancer is one of the most common malignant tumors in China,with its high incidence and high mortality rate.Radical surgery is still the most commonly used and effective treatment for liver cancer at present,but its recurrence rate is as high as 70% five years after surgery.As liver cancer is a more aggressive malignant tumor,it is very easy to occur distant metastasis and recurrence.Therefore,the control of distant metastasis of liver cancer has become one of the key directions of oncology researchers.pramlintide is an adjuvant therapy drug approved by FDA in2005 for type 1 and type 2 diabetes mellitus.It belongs to islet amyloid polypeptide(IAPP);A nonpolymeric isomer of amylin.At present,it has been reported in relevant literature that pancreatic cancer cell lines overexpressed with IAPP show downregulation of proliferation ability,and it is concluded that overexpression of IAPP or use of Pramlintide can improve the drug resistance of pancreatic cancer gemcitabine resistant strains.We take this as the starting point to study and discuss the related effects of Pramlintide on liver cancer.The purpose of this study was to clarify the inhibitory effect of Pramlintide at appropriate concentration on aerobic glycolysis of different liver cancer cell lines,to explore the effects of Pramlintide inhibiting aerobic glycolysis on EMT,proliferation,invasion and migration of liver cancer cell lines,and to clarify the mechanism of Pramlintide regulating biological behavior of liver cancer cell lines.Methods: By ECAR experiment,we demonstrated that Pramlintide has an important effect on the aerobic glycolysis process of different liver cancer cell lines,and the inhibition effect of Pramlintide at the concentration of10mg/L on the EMT phenotype and the ability of cell metastasis and invasion of liver cancer cells was significant.Wave2.6 and Image J were used for data analysis.The changes of proliferation ability of hepatocellular carcinoma cell lines after glycolysis were clearly inhibited by MTS and clonal formation experiments.The apoptosis of hepatocellular carcinoma cell lines after glycolysis was detected by AV-PI assay.Western-Blotting and Transwell related experiments were conducted to determine the changes of Pramlintide on invasion,migration and EMT of hepatocellular carcinoma cell lines.Image J was used for counting and basic data processing and gray value analysis.The changes of biological activity,glycolysis level and biological behavior of hepatocellular carcinoma cells were investigated by reactivating glycolysis experiment.Results: 1.Compared with the control group,different hepatocellular carcinoma cell lines were treated with 10mg/L Pramlintide.The ECAR test results showed that Pramlintide had an ideal inhibitory effect on the aerobic glycolysis process of hepatocellular carcinoma.2.Compared with the control group,Pramlintide could regulate the proliferation and apoptosis of liver cancer cell lines by inhibiting the process of aerobic glycolysis,and the results were statistically significant.3.Compared with the control group,the invasion,migration,EMT and other biological behaviors of hepatocellular carcinoma cell lines were significantly weakened after glycolysis inhibition,and the results were statistically significant through analysis.4.By re-activating glycolysis experiment,we found that adding oligomycin and inhibiting glycolysis for 12 h did not affect the biological activity of cells,while adding pyruvate combined with Daasa-58 culture could significantly restore the glycolysis level.The invasion,metastasis and EMT ability of cells were again changed with the change of glycolysis level,and the results were statistically significant.Conclusion: This study found that Pramlintide inhibited biological behavior of liver cancer by inhibiting aerobic glycolysis of liver cancer cell lines,which may provide a new direction for clinical treatment of liver cancer.Conclusion: In this study,it was found that pramlintide inhibits the biological behavior of hepatic cancer by inhibiting the aerobic glycolysis of hepatic cancer cells,which may provide a new direction for the clinical treatment of hepatic cancer. |
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