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

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.

journal_name

Int J Oncol

authors

Ding N,Cui XX,Gao Z,Huang H,Wei X,Du Z,Lin Y,Shih WJ,Rabson AB,Conney AH,Hu C,Zheng X

doi

10.3892/ijo.2014.2350

subject

Has Abstract

pub_date

2014-06-01 00:00:00

pages

2139-45

issue

6

eissn

1019-6439

issn

1791-2423

journal_volume

44

pub_type

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