hepatocellular carcinoma, metformin

This article aimed to examine the effect of metformin use on improving outcomes after liver-directed therapy in patients with HCC and identify future directions with the adjuvant use of and potential therapeutic agents that operate on similar mechanistic pathways. Databases were queried to identify pertinent articles on metformin's use as an anti-cancer agent in HCC. Eleven studies were included, with five pre-clinical and six clinical studies. The mean overall survival (OS) and progression-free survival were both higher in the locoregional therapy (LRT) + metformin-treated groups...

BACKGROUND: Our previous work shows that increased matrix stiffness not only alters malignant characteristics of hepatocellular carcinoma (HCC) cells, but also attenuates metformin efficacy in treating HCC cells. Here, we identified differential membrane proteins related to matrix stiffness-mediated metformin resistance for better understand therapeutic resistance of metformin in HCC. METHODS: Differential membrane proteins in HCC cells grown on different stiffness substrates before and after metformin intervention were screened and identified using isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with the liquid chromatography-tandem mass spectrometry (LC-MS/MS), then bioinformatic analysis were applied to determine candidate membrane protein and their possible signaling pathway...

BACKGROUND: Statins, metformin, and aspirin have been reported to reduce the incidence of hepatocellular carcinoma (HCC). However, the effect of their perioperative use on survival outcomes of HCC patients following curative liver resection still remains unclear. METHOD: Three hundred and fifty three patients with a first diagnosis of HCC who underwent curative liver resection were included. Propensity score matching analysis with a users: nonusers ratio of 1:2 were performed for each of the medications (statins, metformin, and aspirin)...

Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder among individuals with chronic hepatitis B (CHB), contributing to additional adverse impacts on both hepatic and extrahepatic systems. Existing evidence suggests a potential positive association between CHB and the development of insulin resistance and T2DM. The presence of T2DM in CHB patients is associated with an increased risk of liver fibrosis, cirrhosis, decompensation, and hepatocellular carcinoma (HCC) occurrence. Moreover, it elevates the risk of non-liver cancers and all-cause mortality in this population...

BACKGROUND: Hepatocellular carcinoma (HCC) is among the commonest malignancies associated with significant cancer-related death. The identification of chemo-preventive agents following HCC treatments with the potential to lower the risk of HCC adverse course is intriguing. Metformin, a first-line agent used in the treatment of type 2 diabetes mellitus (T2DM), has been associated with inhibition of HCC growth. AIM: To determine whether metformin can prevent adverse events ( i...

BACKGROUND: Type 2 diabetes (T2DM) can accelerate the progression of cirrhosis. The potential for oral diabetes medications to counteract the mortality and morbidity of chronic liver diseases is unclear. METHODS: We compared the effectiveness of dual metformin and glucagon-like peptide-1 receptor agonists (GLP1-RA) vs. metformin treatment alone in reducing mortality and hepatic complications in cirrhotic patients with T2DM. We evaluated propensity score-matched cohorts of T2DM and cirrhosis patients treated with metformin or dual metformin and GLP1-RA therapy...

Metformin is the most widely used anti-diabetic drug that helps maintain normal blood glucose levels primarily by suppressing hepatic gluconeogenesis in type II diabetic patients. We previously found that metformin induces apoptotic death in H4IIE rat hepatocellular carcinoma cells. Despite its anti-diabetic roles, the effect of metformin on hepatic de novo lipogenesis (DNL) remains unclear. We investigated the effect of metformin on hepatic DNL and apoptotic cell death in H4IIE cells. Metformin treatment stimulated glucose consumption, lactate production, intracellular fat accumulation, and the expressions of lipogenic proteins...

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. There has been significant progress in understanding the risk factors and epidemiology of HCC during the last few decades, resulting in efficient preventative, diagnostic and treatment strategies. Type 2 diabetes mellitus (T2DM) has been demonstrated to be a major risk factor for developing HCC. Metformin is a widely used hypoglycemic agent for patients with T2DM and has been shown to play a potentially beneficial role in improving the survival of patients with HCC...

BACKGROUND: Alcoholic liver disease (ALD) is still increasing and leads to acute liver injury but also liver cirrhosis and subsequent complications such as liver failure or hepatocellular carcinoma (HCC). As most patients fail to achieve alcohol abstinence, it is essential to identify alternative treatment options in order to improve the outcome of ALD patients. METHODS: Evaluating two large cohorts of patients with ALD from the USA and Korea with a total of 12,006 patients, we investigated the effect on survival of aspirin, metformin, metoprolol, dopamine, and dobutamine drugs in patients with ALD between 2000 and 2020...

BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer worldwide, and sorafenib is a first-line drug for the treatment of advanced liver cancer. Resistance to sorafenib has become a major challenge in the treatment of hepatocellular carcinoma, however, studies have shown that metformin can promote ferroptosis and sorafenib sensitivity. Therefore, the aim of this study was to investigate the promotion of ferroptosis and sorafenib sensitivity by metformin via ATF4/STAT3 in hepatocellular carcinoma cells...

BACKGROUND: Examine the association of metformin use and overall survival (OS) in patients with HCC undergoing image-guided liver-directed therapy (LDT): ablation, transarterial chemoembolization (TACE), or Yttrium-90 radioembolization (Y90 RE). METHODS: Using National Cancer Institute Surveillance, Epidemiology, and End Results registry and Medicare claims databases between 2007 and 2016, we identified patients ≥ 66 years who underwent LDT within 30 days of HCC diagnosis...

BACKGROUND AND AIMS: Lenvatinib is a first-line drug commonly used in the treatment of advanced hepatocellular carcinoma (HCC). However, its clinical efficacy is very limited due to drug resistance. Therefore, there is a great need to explore its combination with other agents to achieve better therapeutic effects. Metformin has been demonstrated to show an anti-cancer effect. This study aimed to investigate the combined effect of lenvatinib with metformin in HCC cells both in vitro and in vivo and elucidate the possible molecular mechanisms...

Hepatocellular carcinoma (HCC) is one of the most common cancers, and it is important to elucidate the carcinogenic factors and improve the recurrence and prognosis of HCC patients. Diabetes mellitus (DM) has been reported to be a risk factor for the carcinogenesis of many cancers including HCC, and the mechanism of DM for carcinogenesis is gradually being elucidated. Metformin, a drug for DM, has been reported to have anticancer effects on many cancers, including HCC. Metformin not only suppresses carcinogenesis but also improves the prognosis of recurrence after treatment, and there are many reports on the mechanism of these effects...

Hepatocellular carcinoma (HCC) is estimated to be the third leading cause of cancer-related mortality and is characterized by low survival rates. Nonalcoholic fatty liver disease (NAFLD) is emerging as a leading cause of HCC, whose rates are increasing, owing to the increasing prevalence of NAFLD. The pathogenesis of NAFLD-associated HCC is multifactorial: insulin resistance, obesity, diabetes and the low-grade hepatic inflammation, which characterizes NAFLD, seem to play key roles in the development and progression of HCC...

BACKGROUND: Liver fibrosis usually progresses to liver cirrhosis and even results in hepatocellular carcinoma, which accounts for one million deaths annually worldwide. To date, anti-liver fibrosis drugs for clinical treatment have not yet been approved. Nowadays, as a natural regulator, Relaxin (RLX) has received increased attention because the expression of RLX could deactivate the activation of hepatic stellate cells (aHSCs) and resolve liver fibrosis. However, its application in treatment is limited due to the short half-life in circulation and low accumulation within the target organ...

Emerging evidence has indicated that peroxisome proliferator-activated receptor-gamma coactivator-1α (PPARGC1A) is involved in hepatocellular carcinoma (HCC). However, its detailed function and up- and downstream mechanisms are incompletely understood. In this study, we confirmed that PPAGC1A is lowly expressed in HCC and is associated with poor prognosis using large-scale public datasets and in-house cohorts. PPAGC1A was found to impair the progression and sensitivity of HCC to lenvatinib. Mechanistically, PPAGC1A repressed bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) by inhibiting WNT/β-catenin signaling...

BACKGROUND: Effects of immune checkpoint blockade (ICB) treatment in hepatocellular carcinoma (HCC) are limited. The current study explored the possibility of exploiting tumor metabolic switches to enhance HCC sensitivity to immune therapies. METHODS: Levels of one-carbon (1C) metabolism and the expression of phosphoserine phosphatase (PSPH), an upstream enzyme of 1C pathway, were evaluated in paired non-tumor and tumor tissues from HCC. Underlying mechanisms mediating the role of PSPH in regulating the infiltration of monocytes/macrophages and CD8+ T lymphocytes were studied through both in vitro and in vivo experiments...

BACKGROUND AIMS: SLC25A47 was initially identified as mitochondrial hepatocellular carcinoma (HCC)-downregulated carrier protein, but its physiological functions and transport substrates are unknown. We aimed to investigate the physiological role of SLC25A47 in hepatic metabolism. APPROACH RESULTS: Treatment of hepatocytes with metformin found that metformin can transcriptionally activate the expression of Slc25a47, which is required for AMPKα phosphorylation...

Hepatocellular carcinoma (HCC) is one of the leading causes of death, which deserves further study to reveal the underlying molecular mechanisms. Studies have shown that miR-9 in associated with poor prognosis in HCC patients. However, the mechanisms of transcriptional activation regulation of miR-9 and its role in the malignant progression of HCC have been rarely investigated. Some transcriptional coactivators can form phase-separated condensates at super-enhancers that compartmentalize and concentrate the transcription apparatus to drive robust gene expression...

BACKGROUND: Emerging data suggest that statins, aspirin and metformin may protect against hepatocellular carcinoma (HCC) development. However, prior meta-analyses were limited by heterogeneity and inclusion of studies without adequate adjustment for baseline risks. AIM: To examine by an updated meta-analysis the association between these medications and HCC risk. METHODS: Medline and Embase databases were searched from inception to March 2022 for studies that balanced baseline risks between study groups via propensity score matching or inverse probability of treatment weighting, that reported the impact of statins, aspirin or metformin on HCC risk...