The impact of metformin use on survival in kidney cancer patients with diabetes: a meta-analysis

Li, Yang; Hu, Liangbo; Xia, Qinghong; Yuan, Yongqiang; Yonghua, Mi

doi:10.1007/s11255-017-1548-4

Cited by 32 publications

(14 citation statements)

References 20 publications

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“…This inconformity was also observed in RCC. Several epidemiological studies showed that the use of metformin was not significantly associated with the kidney cancer outcomes as well as the risk of death [ 26 – 31 ], while Tseng et al and Li et al found that metformin use is correlated with improved survival in patients with localized RCC, but not in metastatic RCC [ 32 , 33 ]. Although studies in types of cancers and RCC lines suggested that metformin has remarkable antitumor activities, making metformin seems to be promising as a cancer chemo preventive or therapeutic drug, the fact that metformin might not be effective in reducing the risk of RCC in cancer clinical trials makes it difficult to determine the benefits of metformin in RCC prevention and treatment.…”

Section: Introductionmentioning

confidence: 99%

Valproic acid sensitizes metformin-resistant human renal cell carcinoma cells by upregulating H3 acetylation and EMT reversal

et al. 2018

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BackgroundMetformin (Met) is a widely available diabetic drug and shows suppressed effects on renal cell carcinoma (RCC) metabolism and proliferation. Laboratory studies in RCC suggested that metformin has remarkable antitumor activities and seems to be a potential antitumor drug. But the facts that metformin may be not effective in reducing the risk of RCC in cancer clinical trials made it difficult to determine the benefits of metformin in RCC prevention and treatment. The mechanisms underlying the different conclusions between laboratory experiments and clinical analysis remains unclear. The goal of the present study was to determine whether long-term metformin use can induce resistance in RCC, whether metformin resistance could be used to explain the disaccord in laboratory and clinical studies, and whether the drug valproic acid (VPA), which inhibits histone deacetylase, exhibits synergistic cytotoxicity with metformin and can counteract the resistance of metformin in RCC.MethodsWe performed CCK8, transwell, wound healing assay, flow cytometry and western blotting to detect the regulations of proliferation, migration, cell cycle and apoptosis in 786-O, ACHN and metformin resistance 786-O (786-M-R) cells treated with VPA, metformin or a combination of two drugs. We used TGF-β, SC79, LY294002, Rapamycin, protein kinase B (AKT) inhibitor to treat the 786-O or 786-M-R cells and detected the regulations in TGF-β /pSMAD3 and AMPK/AKT pathways.Results786-M-R was refractory to metformin-induced antitumor effects on proliferation, migration, cell cycle and cell apoptosis. AMPK/AKT pathways and TGF-β/SMAD3 pathways showed low sensibilities in 786-M-R. The histone H3 acetylation diminished in the 786-M-R cells. However, the addition of VPA dramatically upregulated histone H3 acetylation, increased the sensibility of AKT and inhibited pSMAD3/SMAD4, letting the combination of VPA and metformin remarkably reappear the anti-tumour effects of metformin in 786-M-R cells.ConclusionsVPA not only exhibits synergistic cytotoxicity with metformin but also counteracts resistance to metformin in renal cell carcinoma cell. The re-sensitization to metformin induced by VPA in metformin-resistant cells may help treat renal cell carcinoma patients.

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Section: Introductionmentioning

confidence: 99%

Valproic acid sensitizes metformin-resistant human renal cell carcinoma cells by upregulating H3 acetylation and EMT reversal

et al. 2018

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“…The frequency of NSCLC patients concurrent with diabetes is high. Epidemiological studies have shown that metformin can reduce the risk of cancer development and improve the prognosis of certain cancers, such as colorectal cancer, [16] endometrial cancer, [17] pancreatic cancer, [18] and kidney cancer [19] et al Observational studies have attempted to understand the effect of metformin on the prognosis of lung cancer. Some studies have suggested that the use of metformin is associated with an increased risk of death of lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Impact of metformin use on survival outcomes in non-small cell lung cancer treated with platinum

Xin

Xiao²,

Ding³

et al. 2018

Medicine

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Preclinical evidence suggests that metformin, a widely used antidiabetic drug, may have a sensitizing effect on platinum. The purpose of this study was to evaluate the survival outcomes for non-small cell lung cancer (NSCLC) patients with type 2 diabetes mellitus (T2DM) using metformin during platinum-based chemotherapy.The clinicopathological parameters and survival data of 75 NSCLC patients with T2DM from January 2008 to December 2011 were collected and analyzed retrospectively. Patients were divided into 2 groups: metformin exposure group (n = 27) and non-metformin group (patients using other hypoglycemic agents or no drug for controlling n = 48). Univariate and multivariate analyses were performed to assess the association of metformin usage with overall survival (OS).Mean follow-up time was 58.7 months. The mean survival time was 36.74 months in the metformin group and 40.21 months in the non-metformin group. There was no significant difference in survival time between the 2 groups (P = .661). After adjusting gender, age, smoking status, tumor stage, tumor histology, and differentiation, multivariate analysis showed that metformin was not associated with the OS in NSCLC patients treated with concurrent platinum-based chemotherapy (hazard ratio: 1.071, 95% confidence interval: 0.577–1.986, P = .828).Our results indicated that metformin exposure had no significant effect on OS in NSCLC patients treated with platinum-based chemotherapy. Further studies are warranted to evaluate whether metformin could affect the survival of NSCLC patients treated with platinum-based chemotherapy.

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“…Our findings are in line with the meta-analyses on the relationship between metformin use and other cancers. Similarly, they found that metformin use was associated with favorable survival outcomes for patients with kidney, pancreatic, liver, and lung cancer [ 37 – 40 ]. A recently published meta-analysis of six studies also found that metformin users had an improved survival over non-users among endometrial cancer patients (HR, 0.63; 95% CI, 0.45–0.87) [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Metformin use and survival outcomes in endometrial cancer: a systematic review and meta-analysis

Xie

Yang³

et al. 2017

Oncotarget

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Previous studies have evaluated the effects of metformin use on survival outcomes in endometrial cancer, but their results are inconsistent. We conducted a systematic review and meta-analysis to provide a quantitative assessment of the drug's effects based on available evidence. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials to identify relevant studies that evaluated the association between metformin use on survival outcomes in endometrial cancer. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to evaluate the association of metformin use with overall survival and with progression-free survival using a fixed-effects model. A total of nine studies involving 2,016 patients with endometrial cancer were identified. In a meta-analysis of eight studies involving 1,594 individuals, metformin use was associated with significant improvements in overall survival (HR, 0.51; 95% CI, 0.41 to 0.64). Metformin users similarly showed improved progression-free survival in a meta-analysis of two studies involving 632 individuals (HR, 0.63; 95% CI, 0.46 to 0.87). In conclusion, endometrial cancer patients who use metformin show improved overall survival and progression-free survival. Further studies are required to confirm the full potential effects of metformin use on survival outcomes in endometrial cancer.

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The impact of metformin use on survival in kidney cancer patients with diabetes: a meta-analysis

Cited by 32 publications

References 20 publications

Valproic acid sensitizes metformin-resistant human renal cell carcinoma cells by upregulating H3 acetylation and EMT reversal

Valproic acid sensitizes metformin-resistant human renal cell carcinoma cells by upregulating H3 acetylation and EMT reversal

Impact of metformin use on survival outcomes in non-small cell lung cancer treated with platinum

Metformin use and survival outcomes in endometrial cancer: a systematic review and meta-analysis

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