Metformin synergistically enhances antiproliferative effects of cisplatin and etoposide in NCI-H460 human lung cancer cells

Teixeira, Sarah Fernandes; Guimarães, Isabella dos Santos; Madeira, Klesia Pirola; Daltoé, Renata Dalmaschio; Silva, Ian Victor; Rangel, Letícia Batista Azevedo

doi:10.1590/s1806-37132013000600002

Cited by 38 publications

(27 citation statements)

References 20 publications

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“…Through the detection of cell apoptosis markers Bcl‐2 and Bax in the treated or control groups and a data comparison between the different groups, the synergistic effects between metformin and pemetrexed on NSCLC or sensitization effect of metformin to chemotherapy were verified again. Our data demonstrated the relationship between metformin and pemetrexed in treating NSCLC in vitro, which is consistent with the previous findings regarding metformin and other chemicals, such as cisplatin or etoposide .…”

Section: Discussionsupporting

confidence: 92%

Metformin synergistic pemetrexed suppresses non‐small‐cell lung cancer cell proliferation and invasion in vitro

Zhang

Feng

et al. 2017

Cancer Medicine

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The aim of this study was to investigate whether metformin in combination with pemetrexed has an effect on the treatment of non‐small‐cell lung cancer (NSCLC) models and to explore the related molecular mechanism. The half maximal inhibitory concentration (IC50) and combination index (CI) of metformin and pemetrexed were detected by the CCK8 assay to assess the antiproliferative and therapeutic effects of the two‐drug combination. Flow cytometry (FCM) and invasion assays were used to estimate the variation in apoptosis rate and invasion ability of the differently treated NSCLC cell lines. Apoptotic markers were detected by western blotting to validate the data related to the antiproliferation and proapoptosis effects. Metformin monotherapy inhibited the growth of NSCLC cell lines and reduced the invasion ability to different degrees compared with the control groups (P < 0.05). Metformin in combination with pemetrexed produced a synergistic effect (CI < 0.90) compared with the two drugs in monotherapy in the three tested NSCLC cell lines. Metformin in combination with pemetrexed significantly increased the cell numbers of HCC827 cells at S phase (P < 0.001), and the combination therapy had no influence on the A549 and H1975 cell lines. We found that combining metformin with pemetrexed induced more cell apoptosis than metformin or pemetrexed used alone (P < 0.05), which was validated by the apoptotic markers. These results demonstrate that the combination of metformin and pemetrexed has a synergistic effect on the treatment of NSCLC cell lines by inducing apoptosis or blocking the cell cycle. Our data indicate that the combination of metformin and pemetrexed could have beneficial antitumor effects on NSCLC cells in vitro.

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Section: Discussionsupporting

confidence: 92%

Metformin synergistic pemetrexed suppresses non‐small‐cell lung cancer cell proliferation and invasion in vitro

Zhang

Feng

et al. 2017

Cancer Medicine

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“…In addition, it recently gained increasing interest from the medical community due to its potential antitumor effects [ 9 ]. A growing body of data suggests that metformin may elicit antitumor effects alone [ 9 , 10 ] or synergistically improve the response of radiotherapy or chemotherapy [ 9 , 11 , 12 ]. However, recent studies showed an unexpected antagonistic effect of metformin on the cytotoxicity of DDP in vitro [ 13 , 14 ], suggesting that caution should be taken when considering metformin for the treatment of diabetic cancer patients receiving DDP or as a potential adjuvant in DDP-based chemotherapeutic regimens.…”

Section: Introductionmentioning

confidence: 99%

Metformin Synergistically Enhances Cisplatin-Induced Cytotoxicity in Esophageal Squamous Cancer Cells under Glucose-Deprivation Conditions

Bian

et al. 2016

BioMed Research International

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Previous studies suggest that metformin may exert a protective effect on cisplatin-induced cytotoxicity in cancer cells, and this finding has led to a caution for considering metformin use in the treatment of cancer patients. However, in this paper we provide the first demonstration that metformin synergistically augments cisplatin cytotoxicity in the esophageal squamous cancer cell line, ECA109, under glucose-deprivation conditions, which may be more representative of the microenvironment within solid tumors; this effect is very different from the previously reported cytoprotective effect of metformin against cisplatin in commonly used high glucose incubation medium. The potential mechanisms underlying the synergistic effect of metformin on cisplatin-induced cytotoxicity under glucose-deprivation conditions may include enhancement of metformin-associated cytotoxicity, marked reduction in the cellular ATP levels, deregulation of the AKT and AMPK signaling pathways, and impaired DNA repair function.

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“…Furthermore, in a preclinical study, metformin sensitized lung cancer cells to ionizing radiation, which led to an increased response to radiotherapy [41]. Metformin has also been found to exhibit synergistic effects with chemotherapy and target therapy and has thus been studied as an adjuvant treatment for lung cancer [37,[42][43][44][45][46].…”

Section: Discussionmentioning

confidence: 99%

A Cohort Study of Exposure to Antihyperglycemic Therapy and Survival in Patients with Lung Cancer

Danila

Linkeviciute-Ulinskiene

Zablockis

et al. 2020

IJERPH

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We evaluated the effect of antihyperglycemic therapy on the survival of patients with lung cancer (LC). The analysis included patients with LC and concomitant type 2 diabetes. 15,929 patients were classified into five groups: metformin users, insulin users, metformin and insulin users, sulphonylurea users and non-diabetic group. A multivariate analysis showed that exposure to either metformin or to insulin was associated with a lower risk of LC-specific mortality, and this approached statistical significance (HR 0.82, 95% CI 0.72-92 for metformin and HR 0.65, 95% CI 0.44-95 for insulin). When deaths from all causes were considered, only metformin exposure was associated with a significantly lower risk of death (HR 0.82, 95% CI 0.73-0.92). Users of sulphonylurea were at a higher risk of LC-specific and overall mortality (HRs 1.19, 95% CI 0.99-1.43 and 1.22, 95% CI 1.03-1.45). Our study shows a positive effect of metformin on the survival of patients with LC. Moreover, our results show that exposure to insulin was associated with a lower risk of LC-specific mortality, but not with deaths from all causes. The study results suggested that users of sulphonylurea may be at a higher risk of LC-specific and overall mortality.

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Metformin synergistically enhances antiproliferative effects of cisplatin and etoposide in NCI-H460 human lung cancer cells

Cited by 38 publications

References 20 publications

Metformin synergistic pemetrexed suppresses non‐small‐cell lung cancer cell proliferation and invasion in vitro

Metformin synergistic pemetrexed suppresses non‐small‐cell lung cancer cell proliferation and invasion in vitro

Metformin Synergistically Enhances Cisplatin-Induced Cytotoxicity in Esophageal Squamous Cancer Cells under Glucose-Deprivation Conditions

A Cohort Study of Exposure to Antihyperglycemic Therapy and Survival in Patients with Lung Cancer

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