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

Zheng,Xi; Cui,Xiao-Xing; Gao,Zhi; Verano,Michael; Huang,Mou‑Tuan; Liu,Yue; Rabson,Arnold  B.; Conney,Allan  H.

doi:10.3892/ijo.2012.1651

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

Authors:
- Xi Zheng
- Xiao-Xing Cui
- Zhi Gao
- Michael Verano
- Mou‑Tuan Huang
- Yue Liu
- Arnold B. Rabson
- Allan H. Conney
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Affiliations: 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, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China, Child Health Institute of New Jersey, UMDNJ-RWJMS, New Brunswick, NJ 08901; 5Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA
Published online on: October 4, 2012 https://doi.org/10.3892/ijo.2012.1651
Pages: 2269-2275

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Abstract

In the present study, the effects of 12-O-tetradecanoylphorbol-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 synergistically 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.

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