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
October-2017 Volume 14 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-2017 Volume 14 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

Blockade of sonic hedgehog signaling decreases viability and induces apoptosis in retinoblastoma cells: The key role of the PI3K/Akt pathway

  • Authors:
    • Zhidu Song
    • Yuanyuan Du
    • Ying Tao
  • View Affiliations / Copyright

    Affiliations: Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Department of Anesthesiology, The Third Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
    Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4099-4105
    |
    Published online on: August 2, 2017
       https://doi.org/10.3892/ol.2017.6701
  • 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

Retinoblastoma (RB) is the most common type of malignant intraocular cancer in teenagers. One of the proteins abnormally expressed during oncogenesis of RB is sonic hedgehog (SHH), which possesses the capability to selectively activate transcription factors of different genes. However, the detailed function of SHH in RB remains unknown. Thus, the present study sought to investigate the role of SHH in the development of RB. The human RB WERI‑Rb‑1 cell line was used as an in vitro model for the knockdown of SHH by a specific short hairpin RNA (shRNA). To assess the effect of SHH inhibition on cell growth and apoptosis, cell viability, colony formation and flow cytometry assays were conducted. WERI‑Rb‑1 cells transfected with an shRNA targeting SHH were treated with the phosphoinositide‑3 kinase (PI3K)/Akt agonist insulin‑like growth factor 1 (IGF‑1) to investigate the possible mechanism by which SHH promotes RB. The present results revealed that the silencing of SHH induced G1 cell‑cycle arrest and apoptosis in WERI‑Rb‑1 cells and led to a decrease in cell viability, indicating that SHH has a critical role in the determination of RB cell survival. Moreover, according to the results of the IGF‑1 assays, suppression of PI3K/Akt was a prerequisite for SHH inhibition, illuminating its potential role in the treatment of RB. The findings outlined in the present study elucidate a clear link between SHH and the PI3K/Akt pathway in RB cell survival, which could provide valuable inspiration for the advancement of therapies against RB.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Devesa SS: The incidence of retinoblastoma. Am J Ophthalmol. 80:263–265. 1975. View Article : Google Scholar : PubMed/NCBI

2 

Liu Q, Wang Y, Wang H, Liu Y, Liu T and Kunda PE: Tandem therapy for retinoblastoma: Immunotherapy and chemotherapy enhance cytotoxicity on retinoblastoma by increasing apoptosis. J Cancer Res Clin. 139:1357–1372. 2013. View Article : Google Scholar

3 

Broaddus E, Topham A and Singh AD: Survival with retinoblastoma in the USA: 1975–2004. Brit J Ophthalmol. 93:24–27. 2009. View Article : Google Scholar

4 

Milla LA, González-Ramírez CN and Palma V: Sonic Hedgehog in cancer stem cells: A novel link with autophagy. Biol Res. 45:223–230. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Katoh Y and Katoh M: Hedgehog target genes: Mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation. Curr Mol Med. 9:873–886. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Feldmann G, Dhara S, Fendrich V, Bedja D, Beaty R, Mullendore M, Karikari C, Alvarez H, Iacobuzio-Donahue C, Jimeno A, et al: Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: A new paradigm for combination therapy in solid cancers. Cancer Res. 67:2187–2196. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Kasperczyk H, Baumann B, Debatin KM and Fulda S: Characterization of sonic hedgehog as a novel NF-kappaB target gene that promotes NF-kappaB-mediated apoptosis resistance and tumor growth in vivo. FASEB J. 23:21–33. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Ke Z, Caiping S, Qing Z and Xiaojing W: Sonic hedgehog-Gli1 signals promote epithelial-mesenchymal transition in ovarian cancer by mediating PI3K/AKT pathway. Med Oncol. 32:3682015. View Article : Google Scholar : PubMed/NCBI

9 

Choe JY, Yun JY, Jeon YK, Kim SH, Choung HK, Oh S, Park M and Kim JE: Sonic hedgehog signalling proteins are frequently expressed in retinoblastoma and are associated with aggressive clinicopathological features. J Clin Pathol. 68:6–11. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Zheng WH, Kar S, Doré S and Quirion R: Insulin-like growth factor-1 (IGF-1): A neuroprotective trophic factor acting via the Akt kinase pathway. J Neural Transm Suppl. 261–272. 2000.PubMed/NCBI

11 

Hung HC, Hsiao YH and Gean PW: Sonic hedgehog signaling regulates amygdalar neurogenesis and extinction of fear memory. Eur Neuropsychopharmacol. 25:1723–1732. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-(Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Berman DM, Karhadkar SS, Hallahan AR, Pritchard JI, Eberhart CG, Watkins DN, Chen JK, Cooper MK, Taipale J, Olson JM and Beachy PA: Medulloblastoma growth inhibition by hedgehog pathway blockade. Science. 297:1559–1561. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Berman DM, Karhadkar SS, Maitra A, De Montes Oca R, Gerstenblith MR, Briggs K, Parker AR, Shimada Y, Eshleman JR, Watkins DN and Beachy PA: Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature. 425:846–851. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Karhadkar SS, Bova GS, Abdallah N, Dhara S, Gardner D, Maitra A, Isaacs JT, Berman DM and Beachy PA: Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature. 431:707–712. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Thayer SP, di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY, Qi YP, Gysin S, Fernández-del Castillo C, Yajnik V, et al: Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature. 425:851–856. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Watkins DN, Berman DM, Burkholder SG, Wang B, Beachy PA and Baylin SB: Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature. 422:313–317. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Yoo YA, Kang MH, Lee HJ, Kim BH, Park JK, Kim HK, Kim JS and Oh SC: Sonic hedgehog pathway promotes metastasis and lymphangiogenesis via activation of Akt, EMT, and MMP-9 pathway in gastric cancer. Cancer Res. 71:7061–7070. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Mill P, Mo R, Hu MC, Dagnino L, Rosenblum ND and Hui CC: Shh controls epithelial proliferation via independent pathways that converge on N-Myc. Dev Cell. 9:293–303. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Eilers M and Eisenman RN: Myc's broad reach. Genes Dev. 22:2755–2766. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Javelaud D, Pierrat MJ and Mauviel A: Crosstalk between TGF-β and hedgehog signaling in cancer. FEBS Lett. 586:2016–2025. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Yanai K, Nakamura M, Akiyoshi T, Nagai S, Wada J, Koga K, Noshiro H, Nagai E, Tsuneyoshi M, Tanaka M and Katano M: Crosstalk of hedgehog and Wnt pathways in gastric cancer. Cancer Lett. 263:145–156. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Riobo K, Lu X, Ai GM, Haines CP and Emerson CP Jr: Phosphoinositide 3-kinase, Akt are essential for Sonic Hedgehog signaling. Proc Natl Acad Sci USA. 103:4505–4510. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Song Z, Du Y and Tao Y: Blockade of sonic hedgehog signaling decreases viability and induces apoptosis in retinoblastoma cells: The key role of the PI3K/Akt pathway. Oncol Lett 14: 4099-4105, 2017.
APA
Song, Z., Du, Y., & Tao, Y. (2017). Blockade of sonic hedgehog signaling decreases viability and induces apoptosis in retinoblastoma cells: The key role of the PI3K/Akt pathway. Oncology Letters, 14, 4099-4105. https://doi.org/10.3892/ol.2017.6701
MLA
Song, Z., Du, Y., Tao, Y."Blockade of sonic hedgehog signaling decreases viability and induces apoptosis in retinoblastoma cells: The key role of the PI3K/Akt pathway". Oncology Letters 14.4 (2017): 4099-4105.
Chicago
Song, Z., Du, Y., Tao, Y."Blockade of sonic hedgehog signaling decreases viability and induces apoptosis in retinoblastoma cells: The key role of the PI3K/Akt pathway". Oncology Letters 14, no. 4 (2017): 4099-4105. https://doi.org/10.3892/ol.2017.6701
Copy and paste a formatted citation
x
Spandidos Publications style
Song Z, Du Y and Tao Y: Blockade of sonic hedgehog signaling decreases viability and induces apoptosis in retinoblastoma cells: The key role of the PI3K/Akt pathway. Oncol Lett 14: 4099-4105, 2017.
APA
Song, Z., Du, Y., & Tao, Y. (2017). Blockade of sonic hedgehog signaling decreases viability and induces apoptosis in retinoblastoma cells: The key role of the PI3K/Akt pathway. Oncology Letters, 14, 4099-4105. https://doi.org/10.3892/ol.2017.6701
MLA
Song, Z., Du, Y., Tao, Y."Blockade of sonic hedgehog signaling decreases viability and induces apoptosis in retinoblastoma cells: The key role of the PI3K/Akt pathway". Oncology Letters 14.4 (2017): 4099-4105.
Chicago
Song, Z., Du, Y., Tao, Y."Blockade of sonic hedgehog signaling decreases viability and induces apoptosis in retinoblastoma cells: The key role of the PI3K/Akt pathway". Oncology Letters 14, no. 4 (2017): 4099-4105. https://doi.org/10.3892/ol.2017.6701
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