Screening and Validation of a Carvacrol-Targeting Viability-Regulating Protein, SLC6A3, in Liver Hepatocellular Carcinoma.

Background: Liver hepatocellular carcinoma (LIHC) is the second leading cause of tumor-related death in the world. Carvacrol was also found to inhibit multiple cancer types. Here, we proposed that Carvacrol inhibited LIHC. Methods: We used MTT assay to determine the inhibition of Carvacrol on LIHC cells. BATMAN-TCM was used to predict targets of Carvacrol. These targets were further screened by their survival association and expression in cancer using TCGA data. The bioinformatic screened candidates were further validated in in vitro experiments and clinical samples. Finally, docking models of the interaction of Carvacrol and target protein were conducted. Results: Carvacrol inhibited the viability of LIHC cell lines. 40 target genes of Carvacrol were predicted, 8 of them associated with survival. 4 genes were found differentially expressed in LIHC vs. normal liver. Among these genes, the expression of SLC6A3 and SCN4A was found affected by Carvacrol in LIHC cells, but only SLC6A3 correlated with the viability inhibition of Carvacrol on LIHC cell lines. A docking model of the interaction of Carvacrol and SLC6A3 was established with a good binding affinity. SLC6A3 knockdown and expression revealed that SLC6A3 promoted the viability of LIHC cells. Conclusion: Carvacrol inhibited the viability of LIHC cells by downregulating SLC6A3.

Efficacy of re-resection versus radiofrequency ablation for recurrent Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma (HCC) after resection for primary HCC.

BACKGROUND: Whether repeat surgical resection (RSR) or radiofrequency ablation (RFA) is a better option for recurrent hepatocellular carcinoma (HCC) after resection for primary HCC remains controversial. This study was to investigate the clinical efficacy of RSR versus RFA in the treatment of recurrent HCC at Barcelona Clinic Liver Cancer (BCLC) stage 0/A after resection of primary HCC. METHODS: The patients treated by RSR (n=57) or RFA (n=51) for recurrent BCLC stage 0/A HCC in the Affiliated Hospital of Nantong University and Third Affiliated Hospital of Second Military Medical University from January 2008 to March 2018 were included. The general condition, clinicopathological characteristics, and survival were analyzed, and the baseline features and long-term survival were compared between two groups. RESULTS: The baseline characteristics were comparable between two groups. The 1-, 3-, and 5-year survival rates were 96.5%, 80.9%, and 60.6% in RSR group, respectively, and 96.1%, 76.8%, and 59.4% in RFA group, respectively (P=0.48). The 1-, 3-, and 5-year overall survival (OS) rates after treatment for recurrent HCC were 78.9%, 50.5%, and 29.7% in RSR group, respectively, and 80.3%, 50.9%, and 26.0% in RFA group, respectively (P=0.67). The 1-, 3-, and 5-year disease-free survival rates were 68.4%, 39.4%, and 26.6% in RSR group, respectively, and 62.8%, 32.8%, and 20.4% in RFA group, respectively (P=0.55). The incidence of treatment-related complications was significantly higher in the RSR than in the RFA group (42.11% vs. 11.76%, P<0.001). The median hospital stay was significantly shorter in the RFA than in the RSR group (3 vs. 9 days, P<0.001). CONCLUSIONS: RSR and RFA have similar survival benefits in the treatment of recurrent BCLC stage 0/A HCC. RFA is superior to RSR in terms of hospital stay and incidence of treatment-related complications.