Efficacy And Mechanism Of Sorafenib Combined With Coix Seed Oil Injection For Treatment Of Hepatocellular Carcinoma

Background: Hepatocellular carcinoma(HCC)is the most common primary malignancy in the liver diseases(85%-90%).It is the fifth most common cancer in the world and the third leading cause of cancer death.The prognosis of most patients with liver cancer is very poor,and more than 80% of patients are already in advanced stages of treatment or have lost surgical resection.Sorafenib,as an FDA-approved molecular targeted drug for hepatocellular carcinoma,has shown obvious advantages in the treatment of advanced liver cancer.Chinese medicine is a treasure of the motherland medicine.Coix Seed Oil injection has satisfactory curative effect in many cancer treatments.Does Sorafenib combined with Kanglaite injection can further improve the anti-tumor activity and improve the patient's prognosis?Objectives: This study aims to solve the following questions:(1)The therapeutic effects of sorafenib combined with radiofrequency ablation in patients with hepatocellular carcinoma.(2)Compared to the Sorafenib alone,the advantages of Sorafenib combination with Kanglaite injection for hepatocellular carcinoma patients.(3)The potential anti-cancer mechanism of Kanglaite combined with Sorafenib.Methods: A comprehensive search of Pubmed,Cochrane Library,Embase Database,CNKI,Wanfang,Weipu,China Biomedical Literature Database,etc.,to find the clinical research of Sorafenib combined with radiofrequency ablation for hepatocellular carcinoma by using evidence-based meta-analysis methods to evaluate the efficacy of Sorafenib in the treatment of hepatocellular carcinoma.At the same time,we collected patients with advanced hepatocellular carcinoma treated in our hospital from 2016 to 2017.We retrospectively analyzed the efficacy of Sorafenib combined with Kanglaite injection in the treatment of hepatocellular carcinoma.Further cell experiments were performed to study Kanglaite injection combined with sorafenib on hepatoma cell proliferation,invasion,metastasis,and to verify its inhibition of liver cancer cell epithelial-mesenchymal transition.Results:(1)Meta-analysis showed that radiofrequency ablation combined with sorafenib treatment of hepatocellular carcinoma can reduce the 5-year recurrence rate(OR=0.29,95%CI: 0.12-0.70,p=0.004).However,there were no statistically significant difference in overall survival and progress free disease.(2)Retrospective study results suggest that Sorafenib combined with Kang Lai Te injection can improve the median OS in patients with hepatocellular carcinoma(16.683 months,95% CI: 15.374 ~17.991),median PFS(8.984 months,95% CI: 8.166 to 9.803);(3)the results of cell experiment show that Sorafenib combined with Kang Lai Te injection can effectively inhibit the growth of human hepatoma cell line Huh-7 in vitro.The mechanism of action may be through inhibition of cell proliferation,invasion,and migration,which may be related to its inhibition of epithelial-mesenchymal transition of hepatocellular carcinoma cells.Conclusions: Sorafenib combined with Kanglaite injection is a safe and effective treatment for patients with hepatocellular carcinoma.The combination of Chinese medicine Kanglaite injection can significantly increase the antitumor activity of sorafenib,which may be related to its inhibition of hepatoma cell epithelial mesenchymal transition.The conclusion of this study needs further multicenter,large sample,high quality randomized controlled trials to demonstrate.