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 Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
January-2019 Volume 41 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-2019 Volume 41 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

Curcumin attenuates hyperglycemia-driven EGF-induced invasive and migratory abilities of pancreatic cancer via suppression of the ERK and AKT pathways

  • Authors:
    • Wei Li
    • Zheng Wang
    • Xue Xiao
    • Liang Han
    • Zheng Wu
    • Qingyong Ma
    • Lei Cao
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, P.R. China, Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China
  • Pages: 650-658
    |
    Published online on: October 30, 2018
       https://doi.org/10.3892/or.2018.6833
  • 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

The relationship between diabetes mellitus and pancreatic cancer is complex. Diabetes has been postulated to be both an independent risk factor and a consequence of pancreatic cancer. Our previous study confirmed that curcumin plays a vital role in inhibiting the epithelial-mesenchymal transition of pancreatic cancer cells. However, whether curcumin attenuates hyperglycemia-induced cancer invasive and migratory abilities and the underlying mechanisms are not yet well understood. As high glucose is able to induce the expression of epidermal growth factor (EGF), which is intimately related with tumor progression, the aim of this study was to evaluate whether curcumin could influence the high glucose-induced EGF/EGFR pathway and the biological activity of pancreatic cancer cells. Human pancreatic cancer BxPC-3 cells were exposed to high glucose or EGF, with or without curcumin, LY 294002 (an Akt inhibitor) or PD 98059 (an ERK inhibitor). MTT, Transwell invasion and wound healing assays were used to detect the proliferation, invasion and migration potential of cancer cells. The activation of p-EGFR, p-ERK and p-Akt was determined by western blot analysis. The expression levels of uPA and E-cadherin were examined using qRT-PCR and western blot analysis. The results showed that high glucose could not only promote the proliferation, invasion and migration of pancreatic cancer cells, but also induce the expression of EGF and activation of EGFR, ERK and Akt. These effects of high glucose were counter-balanced by curcumin. EGF-induced proliferative, invasive and migratory abilities of BxPC-3 cells were abrogated by curcumin, LY 294002 and PD 98059. In addition, EGF-modulated activation of EGFR, ERK and Akt, as well as the expression of uPA and E-cadherin were inhibited by curcumin. Taken together, the present study indicates that curcumin suppresses hyperglycemia-driven EGF-induced invasion and migration of pancreatic cancer cells by inhibiting the EGF/EGFR signaling pathway and its downstream signaling molecules including ERK and Akt. Curcumin is a potential anticancer agent for pancreatic cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Michl P and Gress TM: Current concepts and novel targets in advanced pancreatic cancer. Gut. 62:317–326. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Bosetti C, Rosato V, Li D, Silverman D, Petersen GM, Bracci PM, Neale RE, Muscat J, Anderson K, Gallinger S, et al: Diabetes, antidiabetic medications, and pancreatic cancer risk: An analysis from the International Pancreatic Cancer Case-Control Consortium. Ann Oncol. 25:2065–2072. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Zhang PH, Chen ZW, Lv D, Xu YY, Gu WL, Zhang XH, Le YL, Zhu HH and Zhu YM: Increased risk of cancer in patients with type 2 diabetes mellitus: A retrospective cohort study in China. BMC Public Health. 12:5672012. View Article : Google Scholar : PubMed/NCBI

6 

Lin QJ, Yang F, Jin C and Fu DL: Current status and progress of pancreatic cancer in China. World J Gastroenterol. 21:7988–8003. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Li J, Ma J, Han L, Xu Q, Lei J, Duan W, Li W, Wang F, Wu E, Ma Q, et al: Hyperglycemic tumor microenvironment induces perineural invasion in pancreatic cancer. Cancer Biol Ther. 16:912–921. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Li W, Zhang L, Chen X, Jiang Z, Zong L and Ma Q: Hyperglycemia promotes the epithelial-mesenchymal transition of pancreatic cancer via hydrogen peroxide. Oxid Med Cell Longev. 2016:51903142016. View Article : Google Scholar : PubMed/NCBI

9 

Appert-Collin A, Hubert P, Crémel G and Bennasroune A: Role of ErbB receptors in cancer cell migration and invasion. Front Pharmacol. 6:2832015. View Article : Google Scholar : PubMed/NCBI

10 

Ardito CM, Grüner BM, Takeuchi KK, Lubeseder-Martellato C, Teichmann N, Mazur PK, Delgiorno KE, Carpenter ES, Halbrook CJ, Hall JC, et al: EGF receptor is required for KRAS-induced pancreatic tumorigenesis. Cancer Cell. 22:304–317. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Han L, Ma Q, Li J, Liu H, Li W, Ma G, Xu Q, Zhou S and Wu E: High glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR. PLoS One. 6:e270742011. View Article : Google Scholar : PubMed/NCBI

12 

Cheng TS, Chen WC, Lin YY, Tsai CH, Liao CI, Shyu HY, Ko CJ, Tzeng SF, Huang CY, Yang PC, et al: Curcumin-targeting pericellular serine protease matriptase role in suppression of prostate cancer cell invasion, tumor growth, and metastasis. Cancer Prev Res (Phila). 6:495–505. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Allegra A, Innao V, Russo S, Gerace D, Alonci A and Musolino C: Anticancer activity of curcumin and its analogues: Preclinical and clinical studies. Cancer Invest. 35:1–22. 2017. View Article : Google Scholar : PubMed/NCBI

14 

Li W, Jiang Z, Xiao X, Wang Z, Wu Z, Ma Q and Cao L: Curcumin inhibits superoxide dismutase-induced epithelial-to-mesenchymal transition via the PI3K/Akt/NF-κB pathway in pancreatic cancer cells. Int J Oncol. 52:1593–1602. 2018.

15 

Cao L, Xiao X, Lei J, Duan W, Ma Q and Li W: Curcumin inhibits hypoxia-induced epithelial-mesenchymal transition in pancreatic cancer cells via suppression of the hedgehog signaling pathway. Oncol Rep. 35:3728–3734. 2016. View Article : Google Scholar : PubMed/NCBI

16 

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

17 

Cao L, Liu J, Zhang L, Xiao X and Li W: Curcumin inhibits H2O2-induced invasion and migration of human pancreatic cancer via suppression of the ERK/NF-κB pathway. Oncol Rep. 36:2245–2251. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Pachmayr E, Treese C and Stein U: Underlying mechanisms for distant metastasis - Molecular biology. Visc Med. 33:11–20. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Wu WS, Wu JR and Hu CT: Signal cross talks for sustained MAPK activation and cell migration: The potential role of reactive oxygen species. Cancer Metastasis Rev. 27:303–314. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Mayer IA and Arteaga CL: The PI3K/AKT pathway as a target for cancer treatment. Annu Rev Med. 67:11–28. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Li W, Ma Z, Ma J, Li X, Xu Q, Duan W, Chen X, Lv Y, Zhou S, Wu E, et al: Hydrogen peroxide mediates hyperglycemia-induced invasive activity via ERK and p38 MAPK in human pancreatic cancer. Oncotarget. 6:31119–31133. 2015.PubMed/NCBI

22 

Jiang WG and Ablin RJ: Cancer metastasis, challenges, progress and the opportunities. Front Biosci (Elite Ed). 3:391–394. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Xue C, Wyckoff J, Liang F, Sidani M, Violini S, Tsai KL, Zhang ZY, Sahai E, Condeelis J and Segall JE: Epidermal growth factor receptor overexpression results in increased tumor cell motility in vivo coordinately with enhanced intravasation and metastasis. Cancer Res. 66:192–197. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Cao L, Chen X, Xiao X, Ma Q and Li W: Resveratrol inhibits hyperglycemia-driven ROS-induced invasion and migration of pancreatic cancer cells via suppression of the ERK and p38 MAPK signaling pathways. Int J Oncol. 49:735–743. 2016. View Article : Google Scholar : PubMed/NCBI

25 

Xu Q, Zong L, Chen X, Jiang Z, Nan L, Li J, Duan W, Lei J, Zhang L, Ma J, et al: Resveratrol in the treatment of pancreatic cancer. Ann NY Acad Sci. 1348:10–19. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Chiang SP, Cabrera RM and Segall JE: Tumor cell intravasation. Am J Physiol Cell Physiol. 311:C1–C14. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Wee P and Wang Z: Epidermal growth factor receptor cell proliferation signaling pathways. Cancers (Basel). 9:92017.

28 

Modjtahedi H and Essapen S: Epidermal growth factor receptor inhibitors in cancer treatment: Advances, challenges and opportunities. Anticancer Drugs. 20:851–855. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Soung YH and Chung J: Curcumin inhibition of the functional interaction between integrin α6β4 and the epidermal growth factor receptor. Mol Cancer Ther. 10:883–891. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Le UM, Hartman A and Pillai G: Enhanced selective cellular uptake and cytotoxicity of epidermal growth factor-conjugated liposomes containing curcumin on EGFR-overexpressed pancreatic cancer cells. J Drug Target. 26:676–683. 2018. View Article : Google Scholar : PubMed/NCBI

31 

Liang Z, Wu R, Xie W, Xie C, Wu J, Geng S, Li X, Zhu M, Zhu W, Zhu J, et al: Effects of curcumin on tobacco smoke-induced hepatic MAPK pathway activation and epithelial-mesenchymal transition In Vivo. Phytother Res. 31:1230–1239. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Zhou X, Su J, Feng S, Wang L, Yin X, Yan J and Wang Z: Antitumor activity of curcumin is involved in down-regulation of YAP/TAZ expression in pancreatic cancer cells. Oncotarget. 7:79076–79088. 2016. View Article : Google Scholar : PubMed/NCBI

33 

Zhang Y, Xue YB, Li H, Qiu D, Wang ZW and Tan SS: Inhibition of cell survival by curcumin is associated with downregulation of cell division cycle 20 (Cdc20) in pancreatic cancer cells. Nutrients. 9:92017. View Article : Google Scholar :

34 

Su J, Zhou X, Wang L, Yin X and Wang Z: Curcumin inhibits cell growth and invasion and induces apoptosis through down-regulation of Skp2 in pancreatic cancer cells. Am J Cancer Res. 6:1949–1962. 2016.PubMed/NCBI

35 

Yoshida K, Toden S, Ravindranathan P, Han H and Goel A: Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating PRC2 subunit EZH2, and the lncRNA PVT1 expression. Carcinogenesis. 38:1036–1046. 2017. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li W, Wang Z, Xiao X, Han L, Wu Z, Ma Q and Cao L: Curcumin attenuates hyperglycemia-driven EGF-induced invasive and migratory abilities of pancreatic cancer via suppression of the ERK and AKT pathways. Oncol Rep 41: 650-658, 2019.
APA
Li, W., Wang, Z., Xiao, X., Han, L., Wu, Z., Ma, Q., & Cao, L. (2019). Curcumin attenuates hyperglycemia-driven EGF-induced invasive and migratory abilities of pancreatic cancer via suppression of the ERK and AKT pathways. Oncology Reports, 41, 650-658. https://doi.org/10.3892/or.2018.6833
MLA
Li, W., Wang, Z., Xiao, X., Han, L., Wu, Z., Ma, Q., Cao, L."Curcumin attenuates hyperglycemia-driven EGF-induced invasive and migratory abilities of pancreatic cancer via suppression of the ERK and AKT pathways". Oncology Reports 41.1 (2019): 650-658.
Chicago
Li, W., Wang, Z., Xiao, X., Han, L., Wu, Z., Ma, Q., Cao, L."Curcumin attenuates hyperglycemia-driven EGF-induced invasive and migratory abilities of pancreatic cancer via suppression of the ERK and AKT pathways". Oncology Reports 41, no. 1 (2019): 650-658. https://doi.org/10.3892/or.2018.6833
Copy and paste a formatted citation
x
Spandidos Publications style
Li W, Wang Z, Xiao X, Han L, Wu Z, Ma Q and Cao L: Curcumin attenuates hyperglycemia-driven EGF-induced invasive and migratory abilities of pancreatic cancer via suppression of the ERK and AKT pathways. Oncol Rep 41: 650-658, 2019.
APA
Li, W., Wang, Z., Xiao, X., Han, L., Wu, Z., Ma, Q., & Cao, L. (2019). Curcumin attenuates hyperglycemia-driven EGF-induced invasive and migratory abilities of pancreatic cancer via suppression of the ERK and AKT pathways. Oncology Reports, 41, 650-658. https://doi.org/10.3892/or.2018.6833
MLA
Li, W., Wang, Z., Xiao, X., Han, L., Wu, Z., Ma, Q., Cao, L."Curcumin attenuates hyperglycemia-driven EGF-induced invasive and migratory abilities of pancreatic cancer via suppression of the ERK and AKT pathways". Oncology Reports 41.1 (2019): 650-658.
Chicago
Li, W., Wang, Z., Xiao, X., Han, L., Wu, Z., Ma, Q., Cao, L."Curcumin attenuates hyperglycemia-driven EGF-induced invasive and migratory abilities of pancreatic cancer via suppression of the ERK and AKT pathways". Oncology Reports 41, no. 1 (2019): 650-658. https://doi.org/10.3892/or.2018.6833
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