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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2269-2275 |
| Number of pages | 7 |
| Journal | International journal of oncology |
| Volume | 41 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 1 2012 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Keywords
- Chemotherapy
- Gemcitabine
- Pancreatic cancer
- Phorbol ester
- c-Jun NH2-terminal kinase
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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.
In: International journal of oncology, Vol. 41, No. 6, 01.12.2012, p. 2269-2275.Research output: Contribution to journal › Article
TY - JOUR
T1 - 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
AU - Zheng, Xi
AU - Cui, Xiao Xing
AU - Gao, Zhi
AU - Verano, Michael
AU - Huang, Mou Tuan
AU - Liu, Yue
AU - Rabson, Arnold B.
AU - Conney, Allan H.
PY - 2012/12/1
Y1 - 2012/12/1
N2 - 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.
AB - 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.
KW - Chemotherapy
KW - Gemcitabine
KW - Pancreatic cancer
KW - Phorbol ester
KW - c-Jun NH2-terminal kinase
UR - http://www.scopus.com/inward/record.url?scp=84869764138&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84869764138&partnerID=8YFLogxK
U2 - 10.3892/ijo.2012.1651
DO - 10.3892/ijo.2012.1651
M3 - Article
C2 - 23041978
AN - SCOPUS:84869764138
VL - 41
SP - 2269
EP - 2275
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 6
ER -