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
January-2015 Volume 11 Issue 1

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
January-2015 Volume 11 Issue 1

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

Induction of autophagy contributes to cisplatin resistance in human ovarian cancer cells

  • Authors:
    • Lingjie Bao
    • Melba C. Jaramillo
    • Zhenbo Zhang
    • Yunxi Zheng
    • Ming Yao
    • Donna D. Zhang
    • Xiaofang Yi
  • View Affiliations / Copyright

    Affiliations: Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China, Department of Pharmacology and Toxicology, University of Arizona, AZ 85721, Arizona, USA, Department of Obstetrics and Gynecology, Shanghai First People's Hospital, Jiaotong University, Shanghai 200080, P.R. China, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, P.R. China
    Copyright: © Bao et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 91-98
    |
    Published online on: October 16, 2014
       https://doi.org/10.3892/mmr.2014.2671
  • 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

Cisplatin resistance is a major challenge in the clinical treatment of ovarian cancer, of which the underlying mechanisms remain unknown. The aim of the present study was to explore the role of autophagy in cisplatin resistance in ovarian cancer cells. A2780cp cisplatin‑resistant ovarian carcinoma cells and the A2780 parental cell line, were used as a model throughout the present study. The cell viability was determined using a water soluble tetrazolium salt‑8 assay, and western blot analysis was performed to determine the protein expression levels of microtubule‑associated protein 1 light chain 3 (LC3 I and LC3 II), and Beclin 1. Beclin 1 small interfering (si)RNA and 3‑methyladenine (3‑MA) were used to determine whether inhibition of autophagy may re‑sensitize cisplatin‑resistant cells to cisplatin. The ultrastructural analysis of autophagosomes was performed using transmission electron microscopy, and apoptosis was measured by flow cytometry. In both A2780cp and A2780 cells, cisplatin induced the formation of autophagosomes and upregulated the expression levels of autophagy protein markers, LC3 II and Beclin 1. However, the levels of autophagy were significantly higher in A2780cp cells, as compared with the A2780 cells. The combined treatment of cisplatin with 3‑MA, the autophagy pharmacological inhibitor, increased the cell death rate, but had no effects on apoptosis, as compared with cisplatin treatment alone in A2780cp cells. However, inhibition of autophagy by siRNA knockdown of Beclin 1 expression enhanced cisplatin‑induced cell death and apoptosis. The findings of the present study suggest that autophagy has a protective role in human ovarian cancer cells, and that targeting autophagy may promote chemotherapeutic sensitivity.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Kim A, Ueda Y, Naka T and Enomoto T: Therapeutic strategies in epithelial ovarian cancer. J Exp Clin Cancer Res. 31:142012. View Article : Google Scholar : PubMed/NCBI

2 

Siddik ZH: Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene. 22:7265–7279. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Galluzzi L, Senovilla L, Vitale I, et al: Molecular mechanisms of cisplatin resistance. Oncogene. 31:1869–1883. 2012. View Article : Google Scholar

4 

Carew JS, Nawrocki ST and Cleveland JL: Modulating autophagy for therapeutic benefit. Autophagy. 3:464–467. 2007. View Article : Google Scholar

5 

Mathew R, Karantza-Wadsworth V and White E: Role of autophagy in cancer. Nat Rev Cancer. 7:961–967. 2007. View Article : Google Scholar

6 

Eskelinen EL and Saftig P: Autophagy: a lysosomal degradation pathway with a central role in health and disease. Biochim Biophys Acta. 1793:664–673. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Mizushima N, Levine B, Cuervo AM and Klionsky DJ: Autophagy fights disease through cellular self-digestion. Nature. 451:1069–1075. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Guo XL, Li D, Hu F, et al: Targeting autophagy potentiates chemotherapy-induced apoptosis and proliferation inhibition in hepatocarcinoma cells. Cancer Lett. 320:171–179. 2012. View Article : Google Scholar : PubMed/NCBI

9 

O’Donovan TR, O’Sullivan GC and McKenna SL: Induction of autophagy by drug-resistant esophageal cancer cells promotes their survival and recovery following treatment with chemotherapeutics. Autophagy. 7:509–524. 2011.PubMed/NCBI

10 

Wu MY, Fu J, Xu J, O’Malley BW and Wu RC: Steroid receptor coactivator 3 regulates autophagy in breast cancer cells through macrophage migration inhibitory factor. Cell Res. 22:1003–1021. 2012. View Article : Google Scholar

11 

Sirichanchuen B, Pengsuparp T and Chanvorachote P: Long-term cisplatin exposure impairs autophagy and causes cisplatin resistance in human lung cancer cells. Mol Cell Biochem. 364:11–18. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Bao LJ, Jaramillo MC, Zhang ZB, et al: Nrf2 induces cisplatin resistance through activation of autophagy in ovarian carcinoma. Int J Clin Exp Pathol. 7:1502–1513. 2014.PubMed/NCBI

13 

Wang CY, Cusack JC Jr, Liu R and Baldwin AS Jr: Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB. Nat Med. 5:412–417. 1999. View Article : Google Scholar : PubMed/NCBI

14 

Gallego MA, Joseph B, Hemström TH, et al: Apoptosis-inducing factor determines the chemoresistance of non-small-cell lung carcinomas. Oncogene. 23:6282–6291. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Yu H, Su J, Xu Y, et al: p62/SQSTM1 involved in cisplatin resistance in human ovarian cancer cells by clearing ubiquitinated proteins. Eur J Cancer. 47:1585–1594. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Kihara A, Kabeya Y, Ohsumi Y and Yoshimori T: Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network. EMBO Rep. 2:330–335. 2001. View Article : Google Scholar : PubMed/NCBI

17 

Kabeya Y, Mizushima N, Ueno T, et al: LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 19:5720–5728. 2000. View Article : Google Scholar : PubMed/NCBI

18 

Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Øvervatn A, Bjørkøy G and Johansen T: p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem. 282:24131–24145. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Mathew R, Karp CM, Beaudoin B, et al: Autophagy suppresses tumorigenesis through elimination of p62. Cell. 137:1062–1075. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Seglen PO and Gordon PB: 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc Natl Acad Sci USA. 79:1889–1892. 1982. View Article : Google Scholar : PubMed/NCBI

21 

Stroikin Y, Dalen H, Lööf S and Terman A: Inhibition of autophagy with 3-methyladenine results in impaired turnover of lysosomes and accumulation of lipofuscin-like material. Eur J Cell Biol. 83:583–590. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Liu D, Yang Y, Liu Q and Wang J: Inhibition of autophagy by 3-MA potentiates cisplatin-induced apoptosis in esophageal squamous cell carcinoma cells. Med Oncol. 28:105–111. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Zou Z, Wu L, Ding H, et al: MicroRNA-30a sensitizes tumor cells to cis-platinum via suppressing Beclin 1-mediated autophagy. J Biol Chem. 287:4148–4156. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Li J, Hou N, Faried A, Tsutsumi S, Takeuchi T and Kuwano H: Inhibition of autophagy by 3-MA enhances the effect of 5-FU-induced apoptosis in colon cancer cells. Ann Surg Oncol. 16:761–771. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Zhu Y, Zhao L, Liu L, et al: Beclin 1 cleavage by caspase-3 inactivates autophagy and promotes apoptosis. Protein Cell. 1:468–477. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Bao L, Jaramillo MC, Zhang Z, Zheng Y, Yao M, Zhang DD and Yi X: Induction of autophagy contributes to cisplatin resistance in human ovarian cancer cells. Mol Med Rep 11: 91-98, 2015.
APA
Bao, L., Jaramillo, M.C., Zhang, Z., Zheng, Y., Yao, M., Zhang, D.D., & Yi, X. (2015). Induction of autophagy contributes to cisplatin resistance in human ovarian cancer cells. Molecular Medicine Reports, 11, 91-98. https://doi.org/10.3892/mmr.2014.2671
MLA
Bao, L., Jaramillo, M. C., Zhang, Z., Zheng, Y., Yao, M., Zhang, D. D., Yi, X."Induction of autophagy contributes to cisplatin resistance in human ovarian cancer cells". Molecular Medicine Reports 11.1 (2015): 91-98.
Chicago
Bao, L., Jaramillo, M. C., Zhang, Z., Zheng, Y., Yao, M., Zhang, D. D., Yi, X."Induction of autophagy contributes to cisplatin resistance in human ovarian cancer cells". Molecular Medicine Reports 11, no. 1 (2015): 91-98. https://doi.org/10.3892/mmr.2014.2671
Copy and paste a formatted citation
x
Spandidos Publications style
Bao L, Jaramillo MC, Zhang Z, Zheng Y, Yao M, Zhang DD and Yi X: Induction of autophagy contributes to cisplatin resistance in human ovarian cancer cells. Mol Med Rep 11: 91-98, 2015.
APA
Bao, L., Jaramillo, M.C., Zhang, Z., Zheng, Y., Yao, M., Zhang, D.D., & Yi, X. (2015). Induction of autophagy contributes to cisplatin resistance in human ovarian cancer cells. Molecular Medicine Reports, 11, 91-98. https://doi.org/10.3892/mmr.2014.2671
MLA
Bao, L., Jaramillo, M. C., Zhang, Z., Zheng, Y., Yao, M., Zhang, D. D., Yi, X."Induction of autophagy contributes to cisplatin resistance in human ovarian cancer cells". Molecular Medicine Reports 11.1 (2015): 91-98.
Chicago
Bao, L., Jaramillo, M. C., Zhang, Z., Zheng, Y., Yao, M., Zhang, D. D., Yi, X."Induction of autophagy contributes to cisplatin resistance in human ovarian cancer cells". Molecular Medicine Reports 11, no. 1 (2015): 91-98. https://doi.org/10.3892/mmr.2014.2671
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