title: 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.
authors.affiliation: Second Xiangya Hospital, Central South University, Changsha 410011, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ding
authors.affiliation: 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.
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Cui
authors.affiliation: 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.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou 510006, P.R. China.
authors.forename: Huarong
authors.initials: H
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Xingchuan
authors.initials: X
authors.lastname: Wei
authors.affiliation: Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou 510006, P.R. China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Du
authors.affiliation: Division of Biometrics, School of Public Health, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Division of Biometrics, School of Public Health, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903, USA.
authors.forename: Weichung Joe
authors.initials: WJ
authors.lastname: Shih
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
authors.forename: Arnold B
authors.initials: AB
authors.lastname: Rabson
authors.affiliation: 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.
authors.forename: Allan H
authors.initials: AH
authors.lastname: Conney
authors.affiliation: Second Xiangya Hospital, Central South University, Changsha 410011, P.R. China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Xi
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D000069059:Atorvastatin; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011720:Pyrazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D011758:Pyrroles / Q000008:administration & dosage* / Q000627:therapeutic use; D015363:Quinolones / Q000008:administration & dosage* / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D006538:Heptanoic Acids; D011720:Pyrazoles; D011758:Pyrroles; D015363:Quinolones; D013449:Sulfonamides; D000069059:Atorvastatin; D000068579:Celecoxib; C402769:tipifarnib