A triple combination of atorvastatin, celecoxib and tipifarnib strongly inhibits pancreatic cancer cells and xenograft pancreatic tumors

  • Authors:
    • Ning Ding
    • Xiao-Xing Cui
    • Zhi Gao
    • Huarong Huang
    • Xingchuan Wei
    • Zhiyun Du
    • Yong Lin
    • Weichung Joe Shih
    • Arnold B. Rabson
    • Allan H. Conney
    • Chunhong Hu
    • Xi Zheng
  • View Affiliations

  • Published online on: March 19, 2014     https://doi.org/10.3892/ijo.2014.2350
  • Pages: 2139-2145
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Because K-Ras mutation and cyclooxygenase-2 (COX-2) overexpression are hallmarks of majority of pancreatic cancer patients, an approach to inhibit the progression and growth of pancreatic cancer using the simultaneous administration of agents that inhibit the function of both targets, should be considered. In the present study, we assessed the effects of atorvastatin (Lipitor), celecoxib (Celebrex) and tipifarnib (Zarnestra) on the growth of human pancreatic cancer. In the in vitro studies, we found that treatment of human pancreatic tumor cells with a combination of atorvastatin, celecoxib and tipifarnib had a stronger inhibitory effect on growth and a stronger stimulatory effect on apoptosis than each drug alone or for any combination of two drugs. We also found that treatment of Panc-1 cells with a combination of all three drugs strongly decreased the levels of phosphorylated Erk1/2 and Akt. In an animal model of xenograft tumors in severe combined immunodeficient (SCID) mice, we found that daily i.p. injections of a combination of atorvastatin, celecoxib and tipifarnib had a stronger inhibitory effect on the growth of the tumors in mice than each drug alone or for any combination of two drugs. The results of our study indicate that a combination of atorvastatin, celecoxib and tipifarnib may be an effective strategy for the treatment of pancreatic cancer.
View Figures
View References

Related Articles

Journal Cover

June-2014
Volume 44 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Ding N, Cui X, Gao Z, Huang H, Wei X, Du Z, Lin Y, Shih WJ, Rabson AB, Conney AH, Conney AH, et al: A triple combination of atorvastatin, celecoxib and tipifarnib strongly inhibits pancreatic cancer cells and xenograft pancreatic tumors. Int J Oncol 44: 2139-2145, 2014
APA
Ding, N., Cui, X., Gao, Z., Huang, H., Wei, X., Du, Z. ... Zheng, X. (2014). A triple combination of atorvastatin, celecoxib and tipifarnib strongly inhibits pancreatic cancer cells and xenograft pancreatic tumors. International Journal of Oncology, 44, 2139-2145. https://doi.org/10.3892/ijo.2014.2350
MLA
Ding, N., Cui, X., Gao, Z., Huang, H., Wei, X., Du, Z., Lin, Y., Shih, W. J., Rabson, A. B., Conney, A. H., Hu, C., Zheng, X."A triple combination of atorvastatin, celecoxib and tipifarnib strongly inhibits pancreatic cancer cells and xenograft pancreatic tumors". International Journal of Oncology 44.6 (2014): 2139-2145.
Chicago
Ding, N., Cui, X., Gao, Z., Huang, H., Wei, X., Du, Z., Lin, Y., Shih, W. J., Rabson, A. B., Conney, A. H., Hu, C., Zheng, X."A triple combination of atorvastatin, celecoxib and tipifarnib strongly inhibits pancreatic cancer cells and xenograft pancreatic tumors". International Journal of Oncology 44, no. 6 (2014): 2139-2145. https://doi.org/10.3892/ijo.2014.2350