TY - JOUR AB - 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. AD - Second Xiangya Hospital, Central South University, Changsha 410011, P.R. China Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou 510006, P.R. China Division of Biometrics, School of Public Health, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903, USA Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA AU - Ding,Ning AU - Cui,Xiao-Xing AU - Gao,Zhi AU - Huang,Huarong AU - Wei,Xingchuan AU - Du,Zhiyun AU - Lin,Yong AU - Shih,Weichung,Joe AU - Rabson,Arnold,B. AU - Conney,Allan,H. AU - Hu,Chunhong AU - Zheng,Xi DA - 2014/06/01 DO - 10.3892/ijo.2014.2350 EP - 2145 IS - 6 JO - Int J Oncol KW - statin cyclooxygenase-2 farnesyl transferase Ras pancreatic cancer PY - 2014 SN - 1019-6439 1791-2423 SP - 2139 ST - A triple combination of atorvastatin, celecoxib and tipifarnib strongly inhibits pancreatic cancer cells and xenograft pancreatic tumors T2 - International Journal of Oncology TI - A triple combination of atorvastatin, celecoxib and tipifarnib strongly inhibits pancreatic cancer cells and xenograft pancreatic tumors UR - https://doi.org/10.3892/ijo.2014.2350 VL - 44 ER -