Impact of metformin on gastric adenocarcinoma survival: A Belgian population based study

Lacroix, Olivia; Couttenier, Alexandra; Vaes, Evelien; Cardwell, Christopher; Schutter, Harlinde De; Robert, Annie

doi:10.1016/j.canep.2018.02.001

Cited by 13 publications

(12 citation statements)

References 34 publications

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“…30 The study based on a Belgian population indicated that metformin improved the overall survival, but not cancer-specific survival. 29 It remains unclear whether metformin would have similar beneficial effects in patients with gastric cancer without DM. Hence, further prospective studies to evaluate metformin’s role as adjuvant therapy in non-DM GC patients are needed.…”

Section: The Efficacy Of Metformin For Gastric Cancer In Clinical Pramentioning

confidence: 99%

<p>Preventative and Therapeutic Effects of Metformin in Gastric Cancer: A New Contribution of an Old Friend</p>

Zhang¹,

Wen²,

Zhou³

et al. 2020

CMAR

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Gastric cancer (GC) is a cancer with high prevalence, and is one of the leading causes of cancer death worldwide. Metformin is a widely used hypoglycemic agent for type-2 diabetes mellitus (T2DM). Recently, metformin has drawn increasing attention in the field of cancer research for its emerging anti-cancer roles. However, the efficacy and underlying molecular mechanisms of metformin in the prevention and treatment for GC remain controversial. This review summarized the present clinical and mechanistic studies that investigated the efficacy of metformin in GC. It was found that the majority of clinical studies affirmed protective roles of metformin in both gastric cancer risk and survival rate. In addition, metformin’s effects in the prevention and treatment for GC involve multiple pathways mainly via AMPK and IGF-1R. It was concluded that metformin presents a unique opportunity for application against GC, but further clinical and mechanistic investigations are required to solidify the roles of metformin in GC.

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Section: The Efficacy Of Metformin For Gastric Cancer In Clinical Pramentioning

confidence: 99%

<p>Preventative and Therapeutic Effects of Metformin in Gastric Cancer: A New Contribution of an Old Friend</p>

Zhang¹,

Wen²,

Zhou³

et al. 2020

CMAR

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“…Comorbidities in the year prior to diagnosis were derived from claims data including in-and 5 outpatient dispensed medication, according to a previously described methodology [18,20]. 6…”

Section: Covariatesmentioning

confidence: 99%

“…32 4 Based on previous studies, we hypothesized that statin use after diagnosis might be associated 1 with a decreased mortality for this cancer type. As described in another report, our data set resulted from the linkage of several databases [18]. 3…”

Section: Introductionmentioning

confidence: 99%

Statin use after diagnosis is associated with an increased survival in esophageal cancer patients: a Belgian population-based study

Lacroix

Couttenier

Vaes³

et al. 2019

Cancer Causes Control

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“…The epidemiological studies have suggested that the use of metformin is associated with a decreased incidence of cancer, and improved prognosis and cancer-associated mortality in patients with T2D (13,14). The anticancer effects of metformin have been reported in breast (15,16), colorectal (17), liver (18), cervical (19), endometrial (20), gastric (21), lung (22), ovarian (23), prostate (24), pancreatic (25) and renal (26) cancer. Various studies have demonstrated that the anticancer mechanisms of metformin are mediated via the AMPK/mammalian target of rapamycin (mTOR) cascade, and the signaling is dependent on AMPK activation leading to inhibition of mTOR that represses protein synthesis, cell proliferation, cell cycle progression and apoptotic cell death (27-29).…”

Section: Introductionmentioning

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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Impact of metformin on gastric adenocarcinoma survival: A Belgian population based study

Cited by 13 publications

References 34 publications

<p>Preventative and Therapeutic Effects of Metformin in Gastric Cancer: A New Contribution of an Old Friend</p>

<p>Preventative and Therapeutic Effects of Metformin in Gastric Cancer: A New Contribution of an Old Friend</p>

Statin use after diagnosis is associated with an increased survival in esophageal cancer patients: a Belgian population-based study

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

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