Triptolide induces apoptosis and inhibits the growth and angiogenesis of human pancreatic cancer cells by downregulating COX-2 and VEGF.
Triptolide (TPL) inhibits the growth and proliferation of a wide range of human cancer cells, but the underlying mechanism is largely unknown. Here, we report that TPL induces apoptosis and inhibits proliferation of PANC-1 pancreatic cancer cells by downregulating cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF). Cell viability and apoptosis were measured by MTT assay and flow cytometry. Real-time PCR and Western blot were used to examine the expression of COX-2 and VEGF. The Matrigel angiogenesis and Transwell migration were employed to assess tube formation and cell migration. Pancreatic cancer mouse xenografts were established to investigate the in vivo antitumor effects of TPL. TUNEL staining and immunohistochemistry were used to detect the apoptosis rate and protein expression in tumor tissues. TPL inhibited the proliferation of pancreatic cancer cells in a time and concentration-dependent manner and decreased the expression of COX-2 and VEGF in vitro. Furthermore, medium from TPL-treated PANC-1 cells inhibited the proliferation, migration, and tube formation of HUVECs. TPL significantly reduced the growth of pancreatic cancer mouse xenografts, accompanied by an induction of apoptosis, inhibition of angiogenesis, and reduction of COX-2 and VEGF. Our data indicate that suppressing the expression of COX-2 and VEGF may be one of the molecular mechanisms by which TPL induces apoptosis and inhibits the growth and angiogenesis of human pancreatic cancer cells.
Department of Gastroenterology, Fudan University, Shanghai, China.
Jian-Xia
JX
Ma
Yun-Liang
YL
Sun
Yi-Qian
YQ
Wang
Hong-Yu
HY
Wu
Jing
J
Jin
Xiao-Feng
XF
Yu
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010616:Phenanthrenes / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D042461:Vascular Endothelial Growth Factor A; C001899:triptolide; D051546:Cyclooxygenase 2