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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
October-2015 Volume 12 Issue 4

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
October-2015 Volume 12 Issue 4

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

GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo

  • Authors:
    • Xiang Zhou
    • Fazheng Shen
    • Pengju Ma
    • Hongyan Hui
    • Sujuan Pei
    • Ming Chen
    • Zhongwei Wang
    • Wenke Zhou
    • Baozhe Jin
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China, Department of Pharmacy, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China
    Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 5641-5646
    |
    Published online on: July 28, 2015
       https://doi.org/10.3892/mmr.2015.4129
  • 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

Glioma is a type of primary malignant tumor of the central nervous system in humans. At present, standard treatment involves surgical resection, followed by radiation therapy and chemotherapy. However, the prognosis is poor and the long‑term survival rate remains low. An improved understanding of the molecular basis for glioma tumorigenesis is in urgently required. The pro‑survival effect of the insulin‑like growth factor (IGF) signaling pathway has been implicated in progression of the glioma disease state. GSK1838705A is a novel, small molecule kinase inhibitor of IGF‑IR, which inhibits IGF signal transduction and downstream target activation. Its anti-proliferative activity has been demonstrated in various tumor cell lines. The present study investigated the potential use of GSK1838705A for the treatment of glioma. Human U87MG glioma cells were used to examine the inhibitory activity of GSK1838705A in cell proliferation, migration and apoptosis. The antitumor activity of GSK1838705A was assessed in a xenograft mouse model. GSK1838705A inhibited the growth and induced the apoptosis of the U87MG glioma cells in a dose‑dependent manner. The GSK1838705A‑treated cells exhibited reduced migratory activity in response to chemoattractants. The present study further demonstrated the antitumor activity of GSK1838705A in vivo. The administration of GSK1838705A significantly inhibited the growth of glioma tumors by inducing the apoptosis of tumor cells. These results suggested that targeting IGF signaling with GSK1838705A may be a promising therapeutic strategy for the treatment of patients with glioma.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Ohgaki H and Kleihues P: Population-based studies on incidence, survival rates and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol. 64:479–489. 2005.PubMed/NCBI

2 

Smoll NR, Gautschi OP, Schatlo B, Schaller K and Weber DC: Relative survival of patients with supratentorial low-grade gliomas. Neuro Oncol. 14:1062–1069. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Spinelli GP, Miele E, Lo Russo G, Miscusi M, Codacci-Pisanelli G, Petrozza V, Papa A, Frati L, Della Rocca C, Gulino A and Tomao S: Chemotherapy and target therapy in the management of adult high-grade gliomas. Curr Cancer Drug Targets. 12:1016–1031. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Wang Y and Jiang T: Understanding high grade glioma: Molecular mechanism, therapy and comprehensive management. Cancer Lett. 331:139–146. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Newlands ES, Stevens MF, Wedge SR, Wheelhouse RT and Brock C: Temozolomide: A review of its discovery, chemical properties, pre-clinical development and clinical trials. Cancer Treat Rev. 23:35–61. 1997. View Article : Google Scholar : PubMed/NCBI

6 

Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, et al: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 10:459–466. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Cao Z, Liu LZ, Dixon DA, Zheng JZ, Chandran B and Jiang BH: Insulin-like growth factor-I induces cyclooxygenase-2 expression via PI3K, MAPK and PKC signaling pathways in human ovarian cancer cells. Cell Signal. 19:1542–1553. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Weroha SJ and Haluska P: The insulin-like growth factor system in cancer. Endocrinol Metab Clin North Am. 41:335–350. vi2012. View Article : Google Scholar : PubMed/NCBI

9 

Jenkins PJ, Frajese V, Jones AM, Camacho-Hubner C, Lowe DG, Fairclough PD, Chew SL, Grossman AB, Monson JP, Besser GM, et al: Insulin-like growth factor I and the development of colorectal neoplasia in acromegaly. J Clin Endocrinol Metab. 85:3218–3221. 2000.PubMed/NCBI

10 

Lukanova A, Lundin E, Toniolo P, Micheli A, Akhmedkhanov A, Rinaldi S, Muti P, Lenner P, Biessy C, Krogh V, et al: Circulating levels of insulin-like growth factor-I and risk of ovarian cancer. Int J Cancer. 101:549–554. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Roddam AW, Allen NE, Appleby P, Key TJ, Ferrucci L, Carter HB, Metter EJ, Chen C, Weiss NS, Fitzpatrick A, et al: Insulin-like growth factors, their binding proteins and prostate cancer risk: Analysis of individual patient data from 12 prospective studies. Ann Intern Med. 149:461–471. W83–W88. 2008. View Article : Google Scholar

12 

Endogenous Hormones and Breast Cancer Collaborative Group; Key TJ, Appleby PN, Reeves GK and Roddam AW: Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3) and breast cancer risk: Pooled individual data analysis of 17 prospective studies. Lancet Oncol. 11:530–542. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Hirano H, Lopes MB, Laws ER Jr, Asakura T, Goto M, Carpenter JE, Karns LR and VandenBerg SR: Insulin-like growth factor-1 content and pattern of expression correlates with histopathologic grade in diffusely infiltrating astrocytomas. Neuro Oncol. 1:109–119. 1999.

14 

Resnicoff M, Sell C, Rubini M, Coppola D, Ambrose D, Baserga R and Rubin R: Rat glioblastoma cells expressing an antisense RNA to the insulin-like growth factor-1 (IGF-1) receptor are nontumorigenic and induce regression of wild-type tumors. Cancer Res. 54:2218–2222. 1994.PubMed/NCBI

15 

Yin S, Girnita A, Strömberg T, Khan Z, Andersson S, Zheng H, Ericsson C, Axelson M, Nistér M, Larsson O, et al: Targeting the insulin-like growth factor-1 receptor by picropodophyllin as a treatment option for glioblastoma. Neuro Oncol. 12:19–27. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Gariboldi MB, Ravizza R and Monti E: The IGFR1 inhibitor NVP-AEW541 disrupts a pro-survival and pro-angiogenic IGF-STAT3-HIF1 pathway in human glioblastoma cells. Biochem Pharmacol. 80:455–462. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Schlenska-Lange A, Knüpfer H, Lange TJ, Kiess W and Knüpfer M: Cell proliferation and migration in glioblastoma multiforme cell lines are influenced by insulin-like growth factor I in vitro. Anticancer Res. 28:1055–1060. 2008.PubMed/NCBI

18 

Sabbatini P, Korenchuk S, Rowand JL, Groy A, Liu Q, Leperi D, Atkins C, Dumble M, Yang J, Anderson K, et al: GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers. Mol Cancer Ther. 8:2811–2820. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Bao NR, Lu M, Bin FW, Chang ZY, Meng J, Zhou LW, Guo T and Zhao JN: Systematic screen with kinases inhibitors reveals kinases play distinct roles in growth of osteoprogenitor cells. Int J Clin Exp Pathol. 6:2082–2091. 2013.PubMed/NCBI

20 

Anisimov VN and Bartke A: The key role of growth hormone-insulin-IGF-1 signaling in aging and cancer. Crit Rev Oncol Hematol. 87:201–223. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Nicoletti I, Migliorati G, Pagliacci MC, Grignani F and Riccardi C: A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods. 139:271–279. 1991. View Article : Google Scholar : PubMed/NCBI

22 

Trojan J, Cloix JF, Ardourel MY, Chatel M and Anthony DD: Insulin-like growth factor type I biology and targeting in malignant gliomas. Neuroscience. 145:795–811. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Freeman DJ, Li AG, Wei G, Li HH, Kertesz N, Lesche R, Whale AD, Martinez-Diaz H, Rozengurt N, Cardiff RD, et al: PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms. Cancer Cell. 3:117–130. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Choe G, Horvath S, Cloughesy TF, Crosby K, Seligson D, Palotie A, Inge L, Smith BL, Sawyers CL and Mischel PS: Analysis of the phosphatidylinositol 3′-kinase signaling pathway in glioblastoma patients in vivo. Cancer Res. 63:2742–2746. 2003.PubMed/NCBI

25 

Ishii N, Maier D, Merlo A, Tada M, Sawamura Y, Diserens AC and Van Meir EG: Frequent co-alterations of TP53, p16/CDKN2A, p14ARF, PTEN tumor suppressor genes in human glioma cell lines. Brain Pathol. 9:469–479. 1999. View Article : Google Scholar : PubMed/NCBI

26 

Poulaki V, Mitsiades CS, McMullan C, Sykoutri D, Fanourakis G, Kotoula V, Tseleni-Balafouta S, Koutras DA and Mitsiades N: Regulation of vascular endothelial growth factor expression by insulin-like growth factor I in thyroid carcinomas. J Clin Endocrinol Metab. 88:5392–5398. 2003. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhou X, Shen F, Ma P, Hui H, Pei S, Chen M, Wang Z, Zhou W and Jin B: GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo. Mol Med Rep 12: 5641-5646, 2015.
APA
Zhou, X., Shen, F., Ma, P., Hui, H., Pei, S., Chen, M. ... Jin, B. (2015). GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo. Molecular Medicine Reports, 12, 5641-5646. https://doi.org/10.3892/mmr.2015.4129
MLA
Zhou, X., Shen, F., Ma, P., Hui, H., Pei, S., Chen, M., Wang, Z., Zhou, W., Jin, B."GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo". Molecular Medicine Reports 12.4 (2015): 5641-5646.
Chicago
Zhou, X., Shen, F., Ma, P., Hui, H., Pei, S., Chen, M., Wang, Z., Zhou, W., Jin, B."GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo". Molecular Medicine Reports 12, no. 4 (2015): 5641-5646. https://doi.org/10.3892/mmr.2015.4129
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou X, Shen F, Ma P, Hui H, Pei S, Chen M, Wang Z, Zhou W and Jin B: GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo. Mol Med Rep 12: 5641-5646, 2015.
APA
Zhou, X., Shen, F., Ma, P., Hui, H., Pei, S., Chen, M. ... Jin, B. (2015). GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo. Molecular Medicine Reports, 12, 5641-5646. https://doi.org/10.3892/mmr.2015.4129
MLA
Zhou, X., Shen, F., Ma, P., Hui, H., Pei, S., Chen, M., Wang, Z., Zhou, W., Jin, B."GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo". Molecular Medicine Reports 12.4 (2015): 5641-5646.
Chicago
Zhou, X., Shen, F., Ma, P., Hui, H., Pei, S., Chen, M., Wang, Z., Zhou, W., Jin, B."GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo". Molecular Medicine Reports 12, no. 4 (2015): 5641-5646. https://doi.org/10.3892/mmr.2015.4129
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