| 【Background】Hepatocarcinoma is the seventh leading cause of death among all cancers worldwide(8.2%)and the fourth leading cause of death among adult men.Among Chinese adults,the death rate of Hepatocarcinoma(13.94%)is higher than the global level,only second to lung cancer(26.99%).Hepatocellular carcinoma(HCC)is not sensitive to chemotherapy and radiotherapy.Sorafenib is still the first-line drug of choice for patients with advanced HCC.Sorafenib,as a classic multi-sites tyrosine kinase inhibitor,mainly blocks the proto-oncogene Ras-Raf-MEK-MAPK pathway.Although sorafenib also has shortcomings in prolonging survival time and HCC cells can develop resistance to it,it plays a cornerstone role in the first-line treatment.The ubiquitin-protease system is a protein degradation system centered on deubiquitinating enzymes,which mainly regulates the degradation of various signal proteins in the cytoplasm.As one of the deubiquitinating enzymes,overexpression of PSMD14 can significantly promote the progression of HCC cells and induce drug resistance in tumor cells.O-phenanthroline(OPA),as a specific inhibitor of PSMD14,can inhibit the growth of HCC cells.【Aims】How to improve the patient’s prognosis and five-year survival rate,as well as improve the efficacy of sorafenib,is a problem that needs to be solved urgently.In this article,OPA and sorafenib are used in HCC cells to explore the possibility of the combination as a new therapy.【Methods and Results】In this study,CCK-8 experiment and clone formation experiment confirm that the combined application of OPA and sorafenib could significantly inhibit the proliferation ability and colony formation ability of HCC cells.We used flow cytometry and Western blot to find that the combination of the two can promote the apoptosis of HCC cells.Finally,OPA can improve the ability of sorafenib to inhibit the invasion and migration of HCC cells through cell migration and invasion experiments.The combination of OPA with sorafenib has shown good effects in HCC cells.OPA can raise the sensitivity of HCC cells to sorafenib.【Conclusions】The development of new drugs or treatment based on existing drug combinations has become a new trend in the treatment of advanced HCC.As a new treatment of the classic drugs sorafenib with OPA,this study can provide a new idea for the therapy of HCC. |
