Potential Benefit of Metformin as Treatment for Colon Cancer: the Evidence so Far

A, Abdel-Satir; Husain, Nazik Elmalaika; Hassan, Abdallah; Elmadhoun, Wadie M; Almobarak, Ahmed O.; Ahmed, Mohamed H.

doi:10.7314/apjcp.2015.16.18.8053

Cited by 13 publications

(15 citation statements)

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“…For example, in vitro and in vivo studies showed that insulin stimulates the growth of colorectal tumors in cell lines ( 6 ) and animal models ( 7 ). Additionally, metformin, a medicine used to regulate glucose homeostasis, suppresses the activity of obesity-related CRC cells ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Mendelian Randomization Study: The Association Between Metabolic Pathways and Colorectal Cancer Risk

et al. 2020

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Background: The roles of obesity-related biomarkers and their molecular pathways in the development of postmenopausal colorectal cancer (CRC) have been inconclusive. We examined insulin resistance (IR) as a major hormonal pathway mediating the association between obesity and CRC risk in a Mendelian randomization (MR) framework. Methods: We performed MR analysis using individual-level data of 11,078 non-Hispanic white postmenopausal women from our earlier genome-wide association study. We identified four independent single-nucleotide polymorphisms associated with fasting glucose (FG), three with fasting insulin (FI), and six with homeostatic model assessment-IR (HOMA-IR), which were not associated with obesity. We estimated hazard ratios (HRs) for CRC by adjusting for potential confounding factors plus genetic principal components. Results: Overall, we observed no direct association between combined 13 IR genetic instruments and CRC risk (HR = 0.96, 95% confidence interval [CI]: 0.78-1.17). In phenotypic analysis, genetically raised HOMA-IR exhibited its effects on the increased risk and FG and FI on the reduced risk for CRC, but with a lack of statistical power. Subgroup analyses by physical activity level and dietary fat intake with combined phenotypes showed that genetically determined IR was associated with reduced CRC risk in both physical activity-stratified (single contributor: MTRR rs722025; HR = 0.12, 95% CI: 0.02-0.62) and high-fat diet subgroups (main contributor: G6PC2 rs560887; HR = 0.59, 95% CI: 0.37-0.94). Conclusions: Complex evidence was observed for a potential causal association between IR and CRC risk. Our findings may provide an additional value of intervention trials to lower IR and reduce CRC risk.

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Section: Introductionmentioning

confidence: 99%

Mendelian Randomization Study: The Association Between Metabolic Pathways and Colorectal Cancer Risk

et al. 2020

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“…Each year, there are over one million newly diagnosed cases and approximately 600,000 cases of colorectal cancer-associated mortality (2). The major risk factors of colorectal cancer are increasing age and lifestyle factors, and other risk factors include obesity, insulin resistance and metabolic syndrome (3). The survival of this disease has improved considerably, however, the 5-year relative survival for patients aged 65 years and older remains as low as 60% (2).…”

Section: Introductionmentioning

confidence: 99%

microRNA-630 promotes cell proliferation and inhibits apoptosis in the HCT116 human colorectal cancer cell line

Zhang

Feng

Zhang

et al. 2017

Molecular Medicine Reports

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Dysregulation of microRNAs (miRNAs) in colorectal cancer provides important opportunities for the development of future miRNA‑based therapies. The present study aimed to assess the role of miRNA‑630 (miR‑630) expression in colorectal cancer. HCT116 human colorectal cancer cells were transfected with miR‑630 inhibitor, mimic or control miRNA, and the effects of miR‑630 dysregulation on cell viability, proliferation and apoptosis were analyzed using MTT and bromodeoxyuridine assays, and an annexin V‑fluorescein isothiocyanate cell apoptosis kit, respectively. In addition, the changes in the protein expression of proliferation‑associated and AKT signaling pathway proteins were analyzed by western blot analysis. The results of the present study demonstrated that overexpression of miR‑630 significantly promoted HCT116 cell proliferation however inhibited apoptosis. Furthermore, miR‑630 overexpression reduced the protein expression of p27, BCL2‑associated X apoptosis regulator, procaspase‑3 and active caspase‑3, and increased the levels of phosphorylated‑AKT and BCL2 apoptosis regulator. The suppression of miR‑630 led to the opposite results. In conclusion, the present findings suggested that miR‑630 may function as an oncogenic miRNA in colorectal cancer, and may promote cellular proliferation and inhibit apoptosis, through the regulation of the expression of p27 and the AKT signaling pathway. The present study suggested that the inhibition of miR‑630 may have potential as an alternative therapeutic strategy for the treatment of patients with colorectal cancer.

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“… 3 Multiple risk factors of CRC include insulin resistance, obesity, low fiber diet, increasing age, black race, smoking, and metabolic syndromes. 3 …”

Section: Introductionmentioning

confidence: 99%

The association between metformin use and colorectal cancer survival among patients with diabetes mellitus: An updated meta‐analysis

Tian

Lei

Liu

et al. 2017

Chronic Diseases and Translational Medicine

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ObjectiveRecent studies have reported conflicting results on the correlation between metformin use and outcomes in patients with colorectal cancer (CRC). A meta-analysis was performed to evaluate the efficacy of metformin therapy on the prognosis of CRC patients with type 2 diabetes mellitus (T2DM).MethodsWe conducted a systematic search of PubMed, EMBASE, the Cochrane Library, and the Web of Science for related articles up to August 2016. Two investigators independently identified and extracted information. Pooled risk estimates [hazard ratios (HRs)] and 95% confidence intervals (CIs) were calculated using fixed-effects models. The risk of publication bias was assessed by examining funnel plot asymmetry as well as Egger's test and Begg's test.ResultsOf 81 articles identified, 8 retrospective cohort studies, representing 6098 cases of CRC patients with T2DM who used metformin and 4954 cases of CRC patients with T2DM who did not use metformin, were included in this meta-analysis. There was no significant heterogeneity and quality difference between studies. Metformin users had significantly improved overall survival (OS) (HR = 0.82, 95% CI: 0.77–0.87, P = 0.000). However, Metformin use cannot affect CRC-specific survival (HR = 0.84, 95% CI: 0.69–1.02, P = 0.079) compared to non-users.ConclusionThis meta-analysis suggests that metformin use may improve survival among CRC patients with T2DM. However, prospective controlled studies are still needed to rigorously evaluate the efficacy of metformin as an anti-tumor agent.

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Potential Benefit of Metformin as Treatment for Colon Cancer: the Evidence so Far

Cited by 13 publications

References 43 publications

Mendelian Randomization Study: The Association Between Metabolic Pathways and Colorectal Cancer Risk

Mendelian Randomization Study: The Association Between Metabolic Pathways and Colorectal Cancer Risk

microRNA-630 promotes cell proliferation and inhibits apoptosis in the HCT116 human colorectal cancer cell line

The association between metformin use and colorectal cancer survival among patients with diabetes mellitus: An updated meta‐analysis

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