Improved Survival in Hepatocellular Carcinoma Patients with Cardiac Arrhythmia by Amiodarone Treatment through Autophagy

Abstract

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. In basic studies, the regulation of autophagy has offered promising results for HCC treatment. This study aimed to address the question of whether amiodarone can improve survival rates in HCC patients associated with autophagy. Using datasets from the National Health Insurance Research Database, we enrolled patients over 18 years of age that had been diagnosed with HCC between January 1997 and December 2010. Amiodarone and non-amiodarone users were matched at a 1:1 frequency, according to all variables. Additionally, HepG2 cells treated with amiodarone were evaluated by cell viability and autophagic change. Autophagic signaling was examined by immunoblotting and tissue array immunohistochemistry. Of the 10,946 patients diagnosed with HCC, each cohort included 221 patients after 1:1 propensity score matching. The median survival was 36.70 months for the amiodarone users, and 24.48 months for the non-amiodarone users. After adjusting for age, gender, comorbidities and treatment, amiodarone users had a significantly lower risk of mortality. Amiodarone users also demonstrated an improved 3-year survival rate. Furthermore, amiodarone treatment-induced autophagy in HepG2 cells was demonstrated by autophagosome formation associated with increasing LC3B-II, P62, and Beclin-1 expression. Autophagic flux also increased following amiodarone treatment with bafilomycin A1. SiRNA of LC3B knocked down endogenous LC3B formation and restored HepG2 cell viability. This study provides epidemiologic evidence that amiodarone via autophagic degradation machinery may offer survival benefits for HCC patients with a history of arrhythmia. Further randomized, blinded, and placebo-controlled trials are warranted for patients with HCC.

Potassium channel-driven bioelectric signalling regulates metastasis in triple-negative breast cancer

“…Amiodarone is a class III anti-arrhythmic drug known to block voltage-gated and inward rectifier K + channels 60À62 and has been shown to improve survival of hepatocellular carcinoma patients. 63 Treatment of MDA-MB-231 and MDA-MB-468 cells with amiodarone at 5 and 10 µM resulted in a significant reduction in 2D cell migration for MDA-MB-231 cells at both concentrations (Fig. 7e) and for MDA-MB-468 cells at 10 µM (Fig.…”

Genetic Alchemy unveiled: MicroRNA-mediated gene therapy as the Artisan craft in the battlefront against hepatocellular carcinoma—a comprehensive chronicle of strategies and innovations

“…Finally, by promoting autophagy-induced miR-224 degradation, the off-label use of amiodarone, a commonly used antiarrhythmic medication, may function as an HCC suppressor ( Huang S.-T. et al, 2019 ).…”

An Insight into the Arising Role of MicroRNAs in Hepatocellular Carcinoma: Future Diagnostic and Therapeutic Approaches

“…Last but not least, the off-label utilization of amiodarone, which constitutes a widely used antiarrhythmic treatment, could be potentially effective as a suppressor agent for HCC, via inducing autophagy-induced miR-224 degradation [ 194 ].…”