TY - JOUR
T1 - Triptolide suppresses 5-lipoxygenase metabolic pathway and induces apoptosis in pancreatic tumor cell lines
AU - Ding, Xiao Ling
AU - Zhou, Guo Xiong
AU - Zhou, Xiao Rong
AU - Wang, Xiao Ying
N1 - Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2008/12
Y1 - 2008/12
N2 - AIM: To investigate the effects and the mechanism of triptolide (TL) on proliferation and apoptosis of pancreatic cancer in vitro. METHODS: Pancreatic tumor cell lines PANC-1, ASPC-1 and SW1990 were treated with different concentrations of TL for 24 h and then, cell death was determined by Typan Blue Staining. Annexin V/PI double staining was performed to evaluate TL-induced apoptosis using flow cytometry. The expression of 5-lipoxygenase (5-LOX) and concentration of its downstream product LTB4 were determined by real time PCR, Western blot and ELISA. 5-LOX cDNA stable transfected SW1990 cells were established successfully. After treatment with TL, it was examined for overexpression of 5-LOX on TL-induced apoptosis. RESULTS: TL induced prominent growth inhibition and apoptosis in human pancreatic cancer cell lines. After treatment at 50 μg/L, the cell viability was 70.5% ± 6.8%, 61.2% ± 5.6% and 52.8% ± 5.3% of PANC-1, ASPC-1 and SW1990, respectively, which were significantly decreased compared with control group (P < 0.05). The apoptosis at 12 h evaluated by AnnexinV positive cells increased in TL-treated group compared with control group (24.2 ± 3.23 vs 9.5 ± 2.18, P < 0.05). TL significantly down-regulated 5-LOX expression in these cell lines and decreased LTB4 concentration in supernatant (P < 0.01, compared with control group). Furthermore, overexpression of 5-LOX in SW1990 cells made them more resistant to TL induced apoptosis, significantly inhibited the TL mediated cell death and apoptosis (P < 0.01 or 0.05, compared with control group). CONCLUSION: Inhibition of 5-LOX pathway of arachidonic acid metabolism is associated with TL's anti-proliferation and pro-apoptotic activity. It also provides evidence that TL has clinic therapeutic value for patients with pancreatic cancer.
AB - AIM: To investigate the effects and the mechanism of triptolide (TL) on proliferation and apoptosis of pancreatic cancer in vitro. METHODS: Pancreatic tumor cell lines PANC-1, ASPC-1 and SW1990 were treated with different concentrations of TL for 24 h and then, cell death was determined by Typan Blue Staining. Annexin V/PI double staining was performed to evaluate TL-induced apoptosis using flow cytometry. The expression of 5-lipoxygenase (5-LOX) and concentration of its downstream product LTB4 were determined by real time PCR, Western blot and ELISA. 5-LOX cDNA stable transfected SW1990 cells were established successfully. After treatment with TL, it was examined for overexpression of 5-LOX on TL-induced apoptosis. RESULTS: TL induced prominent growth inhibition and apoptosis in human pancreatic cancer cell lines. After treatment at 50 μg/L, the cell viability was 70.5% ± 6.8%, 61.2% ± 5.6% and 52.8% ± 5.3% of PANC-1, ASPC-1 and SW1990, respectively, which were significantly decreased compared with control group (P < 0.05). The apoptosis at 12 h evaluated by AnnexinV positive cells increased in TL-treated group compared with control group (24.2 ± 3.23 vs 9.5 ± 2.18, P < 0.05). TL significantly down-regulated 5-LOX expression in these cell lines and decreased LTB4 concentration in supernatant (P < 0.01, compared with control group). Furthermore, overexpression of 5-LOX in SW1990 cells made them more resistant to TL induced apoptosis, significantly inhibited the TL mediated cell death and apoptosis (P < 0.01 or 0.05, compared with control group). CONCLUSION: Inhibition of 5-LOX pathway of arachidonic acid metabolism is associated with TL's anti-proliferation and pro-apoptotic activity. It also provides evidence that TL has clinic therapeutic value for patients with pancreatic cancer.
KW - 5-Lipoxygenase
KW - Pancreatic cancer
KW - Triptolide
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U2 - 10.11569/wcjd.v16.i34.3835
DO - 10.11569/wcjd.v16.i34.3835
M3 - Article
AN - SCOPUS:61349161086
SN - 1009-3079
VL - 16
SP - 3835
EP - 3839
JO - World Chinese Journal of Digestology
JF - World Chinese Journal of Digestology
IS - 34
ER -