Metformin exhibits the anti-proliferation and anti-invasion effects in hepatocellular carcinoma cells after insufficient radiofrequency ablation

Zhang, Qingyun; Kong, Jian; Dong, Shuying; Xu, Wenxiang; Sun, Wenbing

doi:10.1186/s12935-017-0418-6

Cited by 19 publications

(20 citation statements)

References 35 publications

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“…These results are in accordance with those from a study by Valaee et al ( 36 ), indicating that metformin suppresses the proliferation and viability of AGS cells. An in vivo study also demonstrated that metformin did not cause apparent toxicity in nude mice bearing with hepatocellular carcinoma tumors ( 65 ). The findings also revealed that metformin has no effect on viability in normal cells (human colon CCD 841 CoN, embryonic lung HEL 299 and 293 cells).…”

Section: Discussionmentioning

confidence: 99%

Metformin triggers the intrinsic apoptotic response in human AGS gastric adenocarcinoma cells by activating AMPK and suppressing mTOR/AKT signaling

Chiang²,

Tsai

et al. 2019

Int J Oncol

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Metformin is commonly used to treat patients with type 2 diabetes and is associated with a decreased risk of cancer. Previous studies have demonstrated that metformin can act alone or in synergy with certain anticancer agents to achieve anti-neoplastic effects on various types of tumors via adenosine monophosphate-activated protein kinase (AMPK) signaling. However, the role of metformin in AMPK-mediated apoptosis of human gastric cancer cells is poorly understood. In the current study, metformin exhibited a potent anti-proliferative effect and induced apoptotic characteristics in human AGS gastric adenocarcinoma cells, as demonstrated by MTT assay, morphological observation method, terminal deoxynucleotidyl transferase dUTP nick end labeling and caspase-3/7 assay kits. Western blot analysis demonstrated that treatment with metformin increased the phosphorylation of AMPK, and decreased the phosphorylation of AKT, mTOR and p70S6k. Compound C (an AMPK inhibitor) suppressed AMPK phosphorylation and significantly abrogated the effects of metformin on AGS cell viability. Metformin also reduced the phosphorylation of mitogen-activated protein kinases (ERK, JNK and p38). Additionally, metformin significantly increased the cellular ROS level and included loss of mitochondrial membrane potential (ΔΨm). Metformin altered apoptosis-associated signaling to downregulate the BAD phosphorylation and Bcl-2, pro-caspase-9, pro-caspase-3 and pro-caspase-7 expression, and to upregulate BAD, cytochrome c, and Apaf-1 proteins levels in AGS cells. Furthermore, z-VAD-fmk (a pan-caspase inhibitor) was used to assess mitochondria-mediated caspase-dependent apoptosis in metformin-treated AGS cells. The findings demonstrated that metformin induced AMPK-mediated apoptosis, making it appealing for development as a novel anticancer drug for the treating gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Metformin triggers the intrinsic apoptotic response in human AGS gastric adenocarcinoma cells by activating AMPK and suppressing mTOR/AKT signaling

Chiang²,

Tsai

et al. 2019

Int J Oncol

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“…Zhang et al suggested that metformin could block the proliferation and invasion of HCC cells after insufficient radiofrequency ablation. This effect of metformin could be associated with the suppression of Akt survival signaling through AMPK/PTEN [109].…”

Section: Ampk Activators In Hcc Treatmentmentioning

confidence: 99%

The Role of AMP-Activated Protein Kinase as a Potential Target of Treatment of Hepatocellular Carcinoma

Jiang

Tan

Teng

et al. 2019

Cancers

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Background: Hepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide with a very high recurrence rate and very dismal prognosis. Diagnosis and treatment in HCC remain difficult, and the identification of new therapeutic targets is necessary for a better outcome of HCC treatment. AMP-Activated Protein Kinase (AMPK) is an essential intracellular energy sensor that plays multiple roles in cellular physiology and the pathological development of chronic diseases. Recent studies have highlighted the important regulation of AMPK in HCC. This review aims to comprehensively and critically summarize the role of AMPK in HCC. Methods: Original studies were retrieved from NCBI database with keywords including AMPK and HCC, which were analyzed with extensive reading. Results: Dysregulation of the kinase activity and expression of AMPK was observed in HCC, which was correlated with survival of the patients. Loss of AMPK in HCC cells may proceed cell cycle progression, proliferation, survival, migration, and invasion through different oncogenic molecules and pathways. Conclusions: We identified several AMPK activators which may possess potential anti-HCC function, and discussed the clinical perspective on the use of AMPK activators for HCC therapy.

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“…For instance, sorafenib and IFN-α combined with herbal compound inhibited the EMT of HCC cells after iRFA ( 28 , 29 ); bevacizumab inhibited the tumor growth and angiogenesis induced by iRFA ( 30 ); and CTLA-4 blockade suppressed the growth of residual tumors and improved survival in a subcutaneous murine HCC model ( 31 ). Other agents include metformin ( 32 ) and hydroxychloroquine (HCQ) ( 33 ). However, one study demonstrated that ATPase inhibitory factor 1 (IF1) increased HCC cells’ resistance to sorafenib after iRFA ( 16 ).…”

Section: Ablation Therapymentioning

confidence: 99%

Combination of Ablation and Immunotherapy for Hepatocellular Carcinoma: Where We Are and Where to Go

et al. 2021

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Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and is increasing in incidence. Local ablative therapy plays a leading role in HCC treatment. Radiofrequency (RFA) is one of the first-line therapies for early local ablation. Other local ablation techniques (e.g., microwave ablation, cryoablation, irreversible electroporation, phototherapy.) have been extensively explored in clinical trials or cell/animal studies but have not yet been established as a standard treatment or applied clinically. On the one hand, single treatment may not meet the needs. On the other hand, ablative therapy can stimulate local and systemic immune effects. The combination strategy of immunotherapy and ablation is reasonable. In this review, we briefly summarized the current status and progress of ablation and immunotherapy for HCC. The immune effects of local ablation and the strategies of combination therapy, especially synergistic strategies based on biomedical materials, were discussed. This review is hoped to provide references for future researches on ablative immunotherapy to arrive to a promising new era of HCC treatment.

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Metformin exhibits the anti-proliferation and anti-invasion effects in hepatocellular carcinoma cells after insufficient radiofrequency ablation

Cited by 19 publications

References 35 publications

Metformin triggers the intrinsic apoptotic response in human AGS gastric adenocarcinoma cells by activating AMPK and suppressing mTOR/AKT signaling

Metformin triggers the intrinsic apoptotic response in human AGS gastric adenocarcinoma cells by activating AMPK and suppressing mTOR/AKT signaling

The Role of AMP-Activated Protein Kinase as a Potential Target of Treatment of Hepatocellular Carcinoma

Combination of Ablation and Immunotherapy for Hepatocellular Carcinoma: Where We Are and Where to Go

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