Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
September-2015 Volume 10 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2015 Volume 10 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Metformin inhibits growth of lung adenocarcinoma cells by inducing apoptosis via the mitochondria‑mediated pathway

  • Authors:
    • Junling Wang
    • Qiuling Gao
    • Decui Wang
    • Zhiqiang Wang
    • Chun Hu
  • View Affiliations / Copyright

    Affiliations: Department of Medical Oncology, Binzhou Tuberculosis Control Center, Binzhou Medical College, Binzhou, Shandong 250000, P.R. China, Department of Radiology, Binzhou People's Hospital, Binzhou, Shandong 250000, P.R. China, Department of Oncology, RuiJin Hospital, Shanghai JiaoTong University, Shanghai 200001, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1343-1349
    |
    Published online on: July 2, 2015
       https://doi.org/10.3892/ol.2015.3450
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Metformin is commonly used to treat type II diabetes, although it may also reduce the risk of cancer and improve the associated prognosis. However, its mode of action in cancer remains unclear. The present study evaluated the effects of metformin on lung adenocarcinoma A549 cells and identified molecular mechanisms of metformin activity. The A549 cells were treated with metformin at different concentrations and cell viability was assayed by using an MTT assay. The cell cycle and the apoptosis rate were assayed by flow cytometry. Nude mice were transplanted with A549 cells and the tumor growth inhibition rate was detected. Once the A549 cells had been treated with 20 mM metformin for 48 h, the cell cycle was arrested in the G0/Gl phase and the apoptosis rate was 20.57±3.16%. The expression of the B‑cell lymphoma (Bcl)‑2 and Bcl‑extra large proteins was downregulated following metformin treatment, while Bax protein expression was significantly increased. Tumor size in the high‑dose metformin and cisplatin plus metformin groups was significantly smaller, and the inhibition rates were 41.3 and 72.9%, respectively, compared with the control group. These results indicated that metformin displays anticancer activity against lung adenocarcinoma by causing G1 arrest of the cell cycle and subsequent cell apoptosis through the mitochondria‑dependent pathway in A549 cells. Furthermore, it was found that metformin dramatically inhibited lung adenocarcinoma tumor growth in vivo. These data suggest that metformin may become a potential cytotoxic drug in the prevention and treatment of lung adenocarcinoma.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Jemal A, Siegel R, Xu J and Ward E: Cancer statistics, 2010. CA Cancer J Clin. 60:277–300. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Mulshine JL and Sullivan DC: Clinical practice. Lung cancer screening. N Engl J Med. 352:2714–2720. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Dowling RJ, Goodwin PJ and Stambolic V: Understanding the benefit of metformin use in cancer treatment. BMC Med. 9:332011. View Article : Google Scholar : PubMed/NCBI

4 

Evans JM, Donnelly LA, Emslie-Smith AM, et al: Metformin and reduced risk of cancer in diabetic patients. BMJ. 330:1304–1305. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Bowker SL, Majumdar SR, Veugelers P and Johnson JA: Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care. 29:254–258. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Lee MS, Hsu CC, Wahlqvist ML, et al: Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals. BMC Cancer. 11:202011. View Article : Google Scholar : PubMed/NCBI

7 

Zhu Z, Jiang W, Thompson MD, et al: Metformin as an energy restriction mimetic agent for breast cancer prevention. J Carcinog. 10:172011. View Article : Google Scholar : PubMed/NCBI

8 

Schneider MB, Matsuzaki H, Haorah J, et al: Prevention of pancreatic cancer induction in hamsters by metformin. Gastroenterology. 120:1263–1270. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Buzzai M, Jones RG, Amaravadi RK, et al: Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth. Cancer Res. 67:6745–6752. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Dowling RJ, Zakikhani M, Fantus IG, et al: Metformin inhibits mammalian target of rapamycin dependent translation initiation in breast cancer cells. Cancer Res. 67:10804–10812. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Noto H, Goto A, Tsujimoto T and Noda M: Cancer risk in diabetic patients treated with metformin: a systematic review and meta-analysis. PLoS One. 7:e334112012. View Article : Google Scholar : PubMed/NCBI

12 

Shaw RJ, Lamia KA, Vasquez D, et al: The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 310:1642–1646. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Ben Sahra I, Laurent K, Loubat A, et al: The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene. 27:3576–3586. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Zhuang Y and Miskimins WK: Cell cycle arrest in Metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1 and requires p27Kip1 or p21Cip1. J Mol Signal. 3:182008. View Article : Google Scholar : PubMed/NCBI

15 

Vazquez-Martin A, Oliveras-Ferraros C and Menendez JA: The antidiabetic drug metformin suppresses HER2 (erbB-2)oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells. Cell Cycle. 8:88–96. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Bailey CJ and Turner RC: Metformin. N Engl J Med. 334:574–579. 1996. View Article : Google Scholar : PubMed/NCBI

17 

Wang LW, Li ZS, Zou DW, et al: Metformin induces apoptosis of pancreatic cancer cells. World J Gastroenterol. 14:7192–7198. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Hirsch HA, Iliopoulos D, Tsichlis PN and Struhl K: Metformin selectively targets cancer stem cells and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 69:7507–7511. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Cantrell LA, Zhou C, Mendivil A, et al: Metformin is a potent inhibitor of endometrial cancer cell proliferation - implications for a novel treatment strategy. Gynecol Oncol. 116:92–98. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Goodwin PJ, Stambolic V, Lemieux J, et al: Evaluation of metformin in early breast cancer: a modification of the traditional paradigm for clinical testing of anti-cancer agents. Breast Cancer Res Treat. 126:215–220. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Xiong Y, Lu QJ, Zhao J and Wu GY: Metformin inhibits growth of hepatocellular carcinoma cells by inducing apoptosis via mitochondrion-mediated pathway. Asian Pacific J Cancer Prev. 13:3275–3279. 2012. View Article : Google Scholar

22 

Soranna D, Scotti L and Zambon A: Cancer risk associated with use of metformin and sulfonylurea in type 2 diabetes: a meta-analysis. Oncologist. 17:813–822. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Gotlieb WH, Saumet J, Beauchamp MC, et al: In vitro metformin anti-neoplastic activity in epithelial ovarian cancer. Gynecol Oncol. 110:246–250. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Hanna RK, Zhou C, Malloy KM, et al: Metformin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and modulation of the mTOR pathway. Gynecol Oncol. 125:458–469. 2012. View Article : Google Scholar : PubMed/NCBI

25 

An D, Kewalramani G, Chan JK, et al: Metformin influences cardiomyocyte cell death by pathways that are dependent and independent of caspase-3. Diabetologia. 49:2174–2184. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Huang X, Wullschleger S, Shpiro N, et al: Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice. Biochem J. 412:211–221. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Ben Sahra I, Laurent K, Loubat A, et al: The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene. 27:3576–3586. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang J, Gao Q, Wang D, Wang Z and Hu C: Metformin inhibits growth of lung adenocarcinoma cells by inducing apoptosis via the mitochondria‑mediated pathway. Oncol Lett 10: 1343-1349, 2015.
APA
Wang, J., Gao, Q., Wang, D., Wang, Z., & Hu, C. (2015). Metformin inhibits growth of lung adenocarcinoma cells by inducing apoptosis via the mitochondria‑mediated pathway. Oncology Letters, 10, 1343-1349. https://doi.org/10.3892/ol.2015.3450
MLA
Wang, J., Gao, Q., Wang, D., Wang, Z., Hu, C."Metformin inhibits growth of lung adenocarcinoma cells by inducing apoptosis via the mitochondria‑mediated pathway". Oncology Letters 10.3 (2015): 1343-1349.
Chicago
Wang, J., Gao, Q., Wang, D., Wang, Z., Hu, C."Metformin inhibits growth of lung adenocarcinoma cells by inducing apoptosis via the mitochondria‑mediated pathway". Oncology Letters 10, no. 3 (2015): 1343-1349. https://doi.org/10.3892/ol.2015.3450
Copy and paste a formatted citation
x
Spandidos Publications style
Wang J, Gao Q, Wang D, Wang Z and Hu C: Metformin inhibits growth of lung adenocarcinoma cells by inducing apoptosis via the mitochondria‑mediated pathway. Oncol Lett 10: 1343-1349, 2015.
APA
Wang, J., Gao, Q., Wang, D., Wang, Z., & Hu, C. (2015). Metformin inhibits growth of lung adenocarcinoma cells by inducing apoptosis via the mitochondria‑mediated pathway. Oncology Letters, 10, 1343-1349. https://doi.org/10.3892/ol.2015.3450
MLA
Wang, J., Gao, Q., Wang, D., Wang, Z., Hu, C."Metformin inhibits growth of lung adenocarcinoma cells by inducing apoptosis via the mitochondria‑mediated pathway". Oncology Letters 10.3 (2015): 1343-1349.
Chicago
Wang, J., Gao, Q., Wang, D., Wang, Z., Hu, C."Metformin inhibits growth of lung adenocarcinoma cells by inducing apoptosis via the mitochondria‑mediated pathway". Oncology Letters 10, no. 3 (2015): 1343-1349. https://doi.org/10.3892/ol.2015.3450
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team