title: Effects of 12-O-tetradecanoylphorbol-13-acetate in combination with             gemcitabine on Panc-1 pancreatic cancer cells cultured in vitro or Panc-1 tumors             grown in immunodeficient mice.
abstract: In the present study, the effects of 12-O-tetra-decanoylphorbol-13-acetate             (TPA) alone or in combination with gemcitabine on the growth of Panc-1 pancreatic             cancer cells cultured in vitro or grown in NCr immunodeficient nude mice were             investigated. Combinations of TPA and gemcitabine synergi-stically inhibited the             growth and induced apoptosis in Panc-1 cells. The combination of TPA (0.16 nM)             and gemcitabine (0.5 µM) induced a marked increase in phosphorylated c-Jun NH2-terminal             kinase (JNK) in the Panc-1 cells. In animal experiments, NCr nude mice with established             Panc-1 tumors received daily intraperitoneal (i.p.) injections of TPA (50 ng/g             body weight/day) or gemcitabine (0.5 µg/g body weight/day) alone or in combination             for 26 days. Treatment with daily i.p. injections of low doses of TPA or gemcitabine             alone had a modest inhibitory effect on the growth of the tumors. However, the             combination of low doses of TPA and gemcitabine more potently inhibited the growth             of Panc-1 tumors than either agent used individually. Treatment with TPA or gemcitabine             alone or in combination did not affect the body weight of the animals. Clinical             trials with TPA alone or in combination with gemcitabine on patients with pancreatic             cancer are warranted in order to confirm our results.
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. xizheng@pharmacy.rutgers.edu
authors.forename: Xi
authors.initials: X
authors.lastname: Zheng
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Cui
authors.forename: Zhi
authors.initials: Z
authors.lastname: Gao
authors.forename: Michael
authors.initials: M
authors.lastname: Verano
authors.forename: Mou-Tuan
authors.initials: MT
authors.lastname: Huang
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: Arnold B
authors.initials: AB
authors.lastname: Rabson
authors.forename: Allan H
authors.initials: AH
authors.lastname: Conney
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D048670:MAP Kinase Kinase 4; D013755:Tetradecanoylphorbol Acetate; D000093542:Gemcitabine