Aspirin inhibits proliferation of gemcitabine-resistant human pancreatic cancer cells and augments gemcitabine-induced cytotoxicity  

作　　者：Yan-qiu OU Wen bo ZHU Yan LI Peng-xin QIU Yi-jun HUANG Jun XIE Song-min HE Xiao-ke ZHENG Tian-dong LENG Dong XU Guang-mei YAN 

机构地区：[1]Department of Pharmacology, Zhong-shan Medical College, Sun Yat-Sen University, Guangzhou 510089, China

出　　处：《Acta Pharmacologica Sinica》2010年第1期73-80,共8页中国药理学报（英文版）

基　　金：This work was supported by Key program, National Natural Science Foundation of China （No 30830111） and National Natural Science Foundation of China （No 330801408）.

摘　　要：Aim： To investigate whether aspirin is able to augment gemcitabine-induced cytotoxicity in human pancreatic cancer cells. Methods： Two gemcitabine-insensitive human pancreatic cancer cell lines, PANC-1 and Capan-1, were used. Cells were treated with either aspirin or gemcitabine alone or both of them. Cell growth and apoptosis were determined by MTT assay, Annexin V or Hoechest 33258 staining. Cell cycle distribution was examined by flow cytometry. Western blot with specific phosphorylated protein antibodies was used to detect the activation of protein kinase. RT-PCR and Western blot were applied to assess the transcription and protein leve for cyclin D1 and Bcl-2. Results： Aspirin alone significantly inhibits the proliferation of PANC-1 cells by causing cell cycle arrest at G1 phase. Aspirin potentiates the anti-survival effect of gemcitabine as well as its pro-apoptotic effect in PANC-1 cells, although aspirin per se does not trigger apoptosis. Aspirin inhibits GSK-3β activation and suppresses the expression of its downstream gene products （cyclin D1 and Bcl-2）, which are implicated in proliferation, survival and chemoresistance of pancreatic cancer. The effects of aspirin on Capan-1, were similar to that on PANC-1. Conclusion： Our results suggest that aspirin inhibits the proliferation of gemcitabine-resistant pancreatic cancer cells and augments the antisurvival effect of gemcitabine, probably by suppressing the activity of GSK-3β and its downstream gene products.Aim： To investigate whether aspirin is able to augment gemcitabine-induced cytotoxicity in human pancreatic cancer cells. Methods： Two gemcitabine-insensitive human pancreatic cancer cell lines, PANC-1 and Capan-1, were used. Cells were treated with either aspirin or gemcitabine alone or both of them. Cell growth and apoptosis were determined by MTT assay, Annexin V or Hoechest 33258 staining. Cell cycle distribution was examined by flow cytometry. Western blot with specific phosphorylated protein antibodies was used to detect the activation of protein kinase. RT-PCR and Western blot were applied to assess the transcription and protein leve for cyclin D1 and Bcl-2. Results： Aspirin alone significantly inhibits the proliferation of PANC-1 cells by causing cell cycle arrest at G1 phase. Aspirin potentiates the anti-survival effect of gemcitabine as well as its pro-apoptotic effect in PANC-1 cells, although aspirin per se does not trigger apoptosis. Aspirin inhibits GSK-3β activation and suppresses the expression of its downstream gene products （cyclin D1 and Bcl-2）, which are implicated in proliferation, survival and chemoresistance of pancreatic cancer. The effects of aspirin on Capan-1, were similar to that on PANC-1. Conclusion： Our results suggest that aspirin inhibits the proliferation of gemcitabine-resistant pancreatic cancer cells and augments the antisurvival effect of gemcitabine, probably by suppressing the activity of GSK-3β and its downstream gene products.

关 键 词：ASPIRIN human pancreatic cancer GEMCITABINE apoptosis GSK-3Β cyclin D1 Bcl-2 

分 类 号：Q959.133[生物学—动物学] TQ460.72[医药卫生—药物分析学]