Radiosensitizing effect of celecoxib on human pancreatic carcinoma
- VernacularTitle:塞来昔布对胰腺癌的放疗增敏作用及其机制研究
- Author:
Gang XU
;
Xing-Peng WANG
;
Guo-Qi ZHAO
;
Kai WU
;
Song ZHAO
;
- Publication Type:Journal Article
- Keywords:
Pancreatic cancer;
Cyclooxygenase-2;
Apoptosis;
Radiosensitization;
Angiogenesis;
Cell invasion
- From:
Chinese Journal of Digestion
2001;0(11):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the sensitizing effects and the mechanisms of selective cyclooxygenase-2(COX-2)inhibitor celecoxib on radiotherapy of pancreatic cancer.Methods Radiosen- sitization of celecoxib in pancreatic cancer cell SW1990 in vivo and in vitro were investigated by colony forming assay and xenograft tumor model.Expressions of proliferating cell nuclear antigen(PCNA)and Cyelin D1 were assessed by Western Blot.Effect on apoptosis was studied by TUNEL.Expression of bcl-2 and bax was assayed by RT-PCR.Expression and secretion of matrix metalloproteinases(MMPs) and tissue inhibitors of metalloproteinases(TIMPs)were assessed by RT-PCR and zymography.Results Celecoxib enhanced the effect of radiotherapy on pancreatic cancer in vitro and in vivo.TUNEL demonstrated a significant increase of apoptotic cells in vitro after treatment with celecoxib alone or com bined with radiation,but no change after radiation.Expression of bcl-2 was decreased by celecoxib;radi- ation induced the expression of bcl-2;combination of celecoxib and radiation significantly suppressed the expression of bcl-2.In vitro,angiogenesis and cell invasion potential of pancreatic cancer cells were in- hibited by celecoxib,and celecoxib combined with radiation,but without significant change in radiation group compared with the control group.Expression and secretion of MMP-2 and MMP-9 were closely related to the changes in angiogenesis and cell invasion potential,while the expressions of TIMP-1 and TIMP-2 did not alter significantly in all groups.Conclusions The selective eyclooxygenase 2 inhibitor celecoxib potently enhances the effect of radiation on the treatment of pancreatic cancer. Induction of apoptosis,inhibition of angiogenesis and invasion are involved in the mechanism of cele- coxib treatment.
