Statin induces apoptosis of human colon cancer cells and downregulation of insulin-like growth factor 1 receptor via proapoptotic ERK activation

  • Authors:
    • Hyun Joo Jang
    • Eun Mi Hong
    • Se Woo Park
    • Hyun Woo Byun
    • Dong Hee Koh
    • Min Ho Choi
    • Sea Hyub Kae
    • Jin Lee
  • View Affiliations

  • Published online on: May 13, 2016     https://doi.org/10.3892/ol.2016.4569
  • Pages: 250-256
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) signaling plays an important role in tumor progression in patients with certain gastrointestinal tract cancers. In addition to lowering cholesterol in serum, statins have pleiotropic effects, including anti-oxidative, anti‑inflammatory or anti‑neoplastic effects. Therefore, the present study investigated whether statins could induce the apoptosis of colon cancer cells and regulate the expression of IGF‑1R and its associated signaling pathways in the present study. It was demonstrated that simvastatin and pravastatin suppressed cell proliferation and induced cell death in human HT‑29 cells, but simvastatin was more potent than pravastatin. Simvastatin induced apoptosis in a concentration‑dependent manner. In addition, simvastatin suppressed the expression of IGF‑1R and inhibited the activity of phosphorylated‑extracellular signal‑regulated kinase (ERK)1/2 and phosphorylated‑Akt activated by IGF‑1. Simvastatin and IGF‑1 each stimulated the activity of phosphorylated ERK1/2. However, simvastatin inhibited cell proliferation and IGF‑1 stimulated cell proliferation. Mevalonic acid and PD98059 reversed the ERK activation and apoptosis induced by treatment with simvastatin. It was concluded that simvastatin induces the apoptosis of human colon cancer cells and inhibits IGF‑1‑induced ERK and Akt expression via the downregulation of IGF‑1R expression and proapoptotic ERK activation. Simvastatin may be beneficial for the treatment of colon cancer. The present study suggested that statin may possess therapeutic potential for the treatment of colon cancer.
View Figures
View References

Related Articles

Journal Cover

July-2016
Volume 12 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Jang HJ, Hong EM, Park SW, Byun HW, Koh DH, Choi MH, Kae SH and Lee J: Statin induces apoptosis of human colon cancer cells and downregulation of insulin-like growth factor 1 receptor via proapoptotic ERK activation. Oncol Lett 12: 250-256, 2016
APA
Jang, H.J., Hong, E.M., Park, S.W., Byun, H.W., Koh, D.H., Choi, M.H. ... Lee, J. (2016). Statin induces apoptosis of human colon cancer cells and downregulation of insulin-like growth factor 1 receptor via proapoptotic ERK activation. Oncology Letters, 12, 250-256. https://doi.org/10.3892/ol.2016.4569
MLA
Jang, H. J., Hong, E. M., Park, S. W., Byun, H. W., Koh, D. H., Choi, M. H., Kae, S. H., Lee, J."Statin induces apoptosis of human colon cancer cells and downregulation of insulin-like growth factor 1 receptor via proapoptotic ERK activation". Oncology Letters 12.1 (2016): 250-256.
Chicago
Jang, H. J., Hong, E. M., Park, S. W., Byun, H. W., Koh, D. H., Choi, M. H., Kae, S. H., Lee, J."Statin induces apoptosis of human colon cancer cells and downregulation of insulin-like growth factor 1 receptor via proapoptotic ERK activation". Oncology Letters 12, no. 1 (2016): 250-256. https://doi.org/10.3892/ol.2016.4569