Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells.
Pancreatic cancer is a fatal human malignancy associated with an exceptionally poor prognosis. Novel therapeutic strategies are urgently required to treat this disease. In addition to immunosuppressive activity, triptolide possesses strong antitumor activity and synergistically enhances the antitumor activities of conventional chemotherapeutic drugs in preclinical models of pancreatic cancer. The present study investigated the antitumor effects of triptolide in pancreatic cancer cells, either in combination with gemcitabine, or alone. The pancreatic cancer BxPC-3 and PANC-1 cell lines were treated with triptolide, which resulted in time- and dose-dependent growth arrest. When incorporated into a sequential schedule, triptolide synergistically increased gemcitabine-induced cell growth inhibition and apoptosis, in addition to the cooperative regulation of B-cell lymphoma 2 family proteins and loss of mitochondrial membrane potential. Furthermore, triptolide enhanced gemcitabine-induced S phase arrest and DNA double-strand breaks, possibly through checkpoint kinase 1 suppression. The results of the present study suggest that triptolide has therapeutic potential for the treatment of pancreatic cancer, particularly when administered in combination with gemcitabine.
Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing 100850, P.R. China; Medical Research Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China.
Zhixin
Z
Qiao
Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing 100850, P.R. China.
Min
M
He
Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing 100850, P.R. China; College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100022, P.R. China.
M U
MU
He
Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing 100850, P.R. China.
Weijing
W
Li
Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing 100850, P.R. China.
Xuanlin
X
Wang
Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing 100850, P.R. China; College of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China.
Yanbing
Y
Wang
Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing 100850, P.R. China.
Qiyuan
Q
Kuai
Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing 100850, P.R. China; College of Life Science, Northeast Normal University, Changchun, Jilin 130024, P.R. China.
Changlan
C
Li
Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing 100850, P.R. China.
Suping
S
Ren
Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing 100850, P.R. China.
Qun
Q
Yu
DNA damage; apoptosis; gemcitabine; pancreatic cancer; triptolide