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Inhibition of AKT Enhances the Sensitivity of NSCLC Cells to Metformin
CONCLUSION: Inhibition of AKT can enhance the antitumor effect of metformin and would be a promising strategy to sensitize non-small-cell lung cancer to a combination of metformin with radiation or cisplatin.PMID:34230143 | DOI:10.21873/anticanres.15135
Source: Cell Research - July 7, 2021 Category: Cytology Authors: Se-Kyeong Jang Sung-Eun Hong DA-Hee Lee Ji Yea Kim Ji-Young Kim Jungil Hong In-Chul Park Hyeon-Ok Jin Source Type: research

Cancers, Vol. 13, Pages 739: Metformin Reduces Histone H3K4me3 at the Promoter Regions of Positive Cell Cycle Regulatory Genes in Lung Cancer Cells
This study aimed at understanding the effect of metformin on histone H3 methylation, DNA methylation, and chromatin accessibility in lung cancer cells. Metformin significantly reduced H3K4me3 level at the promoters of positive cell cycle regulatory genes such as CCNB2, CDK1, CDK6, and E2F8. Eighty-eight genes involved in cell cycle showed reduced H3K4me3 levels in response to metformin, and 27% of them showed mRNA downregulation. Metformin suppressed the expression of H3K4 methyltransferases MLL1, MLL2, and WDR82. The siRNA-mediated knockdown of MLL2 significantly downregulated global H3K4me3 level and inhibited lung cance...
Source: Cancers - February 10, 2021 Category: Cancer & Oncology Authors: Dongho Kim Yujin Kim Bo Bin Lee Eun Yoon Cho Joungho Han Young Mog Shim Duk-Hwan Kim Tags: Article Source Type: research

Metformin ‐sensitized NSCLC cells to osimertinib via AMPK‐dependent autophagy inhibition
ConclusionMetformin inhibited autophagy and enhanced osimertinib sensitivity via inducing AMPK activation in a time ‐dependent manner.
Source: The Clinical Respiratory Journal - October 6, 2019 Category: Respiratory Medicine Authors: Hengyi Chen, Caiyu Lin, Conghua Lu, Yubo Wang, Rui Han, Li Li, Shuai Hao, Yong He Tags: ORIGINAL ARTICLE Source Type: research

Metformin sensitized NSCLC cells to Osimertinib via AMPK ‐dependent autophagy inhibition
ConclusionMetformin inhibited autophagy and enhanced osimertinib sensitivity via inducing AMPK activation in a time ‐dependent manner.
Source: The Clinical Respiratory Journal - September 27, 2019 Category: Respiratory Medicine Authors: Hengyi Chen, Caiyu Lin, Conghua Lu, Yubo Wang, Rui Han, Li Li, Shuai Hao, Yong He Tags: ORIGINAL ARTICLE Source Type: research

Myeloid Derived Suppressor Cells Interactions With Natural Killer Cells and Pro-angiogenic Activities: Roles in Tumor Progression
Conclusions MDSC are major players in the immunosuppressive scenario in cancer, thanks to their phenotype heterogeneity and critical interaction with several innate immune cells, thus representing a crucial target in oncology. Here we reviewed the interactions of MDSCs with NK cells. The contribution of key cytokines, chemokines and mediators active in this process have been discussed. We also described the contribution of MDSC on angiogenesis directly or indirectly through interactions with NK and immunosuppressive activities. A parallel of the cancer associated to the decidual counterpart of these cells is discussed, a...
Source: Frontiers in Immunology - April 17, 2019 Category: Allergy & Immunology Source Type: research

Cisplatin resistance involves a metabolic reprogramming through ROS and PGC-1 α in NSCLC which can be overcome by OXPHOS inhibition.
CONCLUSION: These results describe a new cisplatin resistance mechanism in NSCLC based on a metabolic reprogramming that is therapeutically exploitable through PGC-1α downregulation or OXPHOS inhibitors. PMID: 30880247 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - March 13, 2019 Category: Biology Authors: Cruz-Bermúdez A, Laza-Briviesca R, Vicente-Blanco RJ, García-Grande A, Coronado MJ, Laine-Menéndez S, Palacios-Zambrano S, Moreno-Villa MR, Ruiz-Valdepeñas AM, Lendinez C, Romero A, Franco F, Calvo V, Alfaro C, Acosta PM, Salas C, Garcia JM, Provencio Tags: Free Radic Biol Med Source Type: research

Metformin inhibits growth of human non-small cell lung cancer cells via liver kinase B-1-independent activation of adenosine monophosphate-activated protein kinase.
Authors: Guo Q, Liu Z, Jiang L, Liu M, Ma J, Yang C, Han L, Nan K, Liang X Abstract Metformin, the most widely administered oral anti‑diabetic therapeutic agent, exerts its glucose-lowering effect predominantly via liver kinase B1 (LKB1)-dependent activation of adenosine monophosphate-activated protein kinase (AMPK). Accumulating evidence has demonstrated that metformin possesses potential antitumor effects. However, whether the antitumor effect of metformin is via the LKB1/AMPK signaling pathway remains to be determined. In the current study, the effects of metformin on proliferation, cell cycle progression, and...
Source: Molecular Medicine Reports - February 9, 2016 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

Repression of phosphoinositide-dependent protein kinase 1 expression by ciglitazone via Egr-1 represents a new approach for inhibition of lung cancer cell growth
Conclusion: Collectively, our results demonstrate that ciglitazone inhibits PDK1 expression through AMPKalpha-mediated induction of Egr-1 and Egr-1 binding to the specific DNA site in the PDK1 gene promoter, which is independent of PPARgamma. Activation of AMPKalpha by metformin enhances the effect of ciglitazone. In turn, this leads to inhibition of NSCLC cell proliferation.
Source: Epidemiologic Perspectives and Innovations - June 13, 2014 Category: Epidemiology Authors: SWei Sunny HannQing TangFang ZhengShunyu ZhaoJianping ChenZhiYu Wang Source Type: research

Inhibition of p38 MAPK-dependent MutS homologue-2 (MSH2) expression by metformin enhances gefitinib-induced cytotoxicity in human squamous lung cancer cells
Conclusion: Together, down-regulation of MSH2 expression can be a possible strategy to enhance the sensitivity of gefitinib to human lung squamous cancer cells.
Source: Lung Cancer - October 17, 2013 Category: Cancer & Oncology Authors: Jen-Chung Ko, Hsien-Chun Chiu, Ting-Yu Wo, Yi-Jhen Huang, Sheng-Chieh Tseng, Yu-Ching Huang, Huang-Jen Chen, Jhan-Jhang Syu, Chien-Yu Chen, Yun-Ting Jian, Yi-Jun Jian, Yun-Wei Lin Tags: Carcinogenesis and molecular biology Source Type: research

Metformin Enhances Cisplatin Cytotoxicity by Suppressing Stat3 Activity Independently of the LKB1-AMPK Pathway.
This study demonstrated a correlation between Stat3 phosphorylation and cisplatin cytotoxicity using AS2 (PC14PE6/AS2)-derived cell lines (AS2/S3C) that contained constitutively active Stat3 plasmids as a model. A Stat3 inhibitor (JSI-124) enhanced the cisplatin sensitivity in AS2 cells, whereas metformin inhibited Stat3 phosphorylation and enhanced cisplatin cytotoxicity. By contrast, another AMPK activator (AICAR) failed to produce these effects. LKB1-AMPK silencing by siRNA or mTOR inhibition by rapamycin or pp242 did not alter the effect of metformin on Stat3 activity suppression, suggesting that metformin can modulate...
Source: American Journal of Respiratory Cell and Molecular Biology - March 22, 2013 Category: Molecular Biology Authors: Lin CC, Yeh HH, Huang WL, Yan JJ, Lai WW, Su WP, Chen HH, Su WC Tags: Am J Respir Cell Mol Biol Source Type: research

Metformin Induces Cytotoxicity by Down‐Regulating Thymidine Phosphorylase and Excision Repair Cross‐Complementation 1 Expression in Non‐Small Cell Lung Cancer Cells
In conclusion, metformin induces cytotoxicity by down‐regulating TP and ERCC1 expression in NSCLC cells.
Source: Basic and Clinical Pharmacology and Toxicology - March 21, 2013 Category: Drugs & Pharmacology Authors: Jen‐Chung Ko, Yu‐Ching Huang, Huang‐Jen Chen, Sheng‐Chieh Tseng, Hsien‐Chun Chiu, Ting‐Yu Wo, Yi‐Jhen Huang, Shao‐Hsing Weng, Robin Y. Y. Chiou, Yun‐Wei Lin Tags: Original Article Source Type: research

Metformin Induces Cytotoxicity by Down‐Regulating Thymidine Phosphorylase and ERCC1 Expression in Non‐Small Cell Lung Cancer Cells
In conclusion, metformin induces cytotoxicity by down‐regulating TP and ERCC1 expression in NSCLC cells.
Source: Basic and Clinical Pharmacology and Toxicology - January 31, 2013 Category: Drugs & Pharmacology Authors: Jen‐Chung Ko, Yu‐Ching Huang, Huang‐Jen Chen, Sheng‐Chieh Tseng, Hsien‐Chun Chiu, Ting‐Yu Wo, Yi‐Jhen Huang, Shao‐Hsing Weng, Robin Y.Y. Chiou, Yun‐Wei Lin Tags: Original Article Source Type: research