Cordycepin Induces S Phase Arrest and Apoptosis in Human Gallbladder Cancer Cells
Xu-An Wang,
Shan-Shan Xiang,
Huai-Feng Li,
Xiang-Song Wu,
Mao-Lan Li,
Yi-Jun Shu,
Fei Zhang,
Yang Cao,
Yuan-Yuan Ye,
Run-Fa Bao,
Hao Weng,
Wen-Guang Wu,
Jia-Sheng Mu,
Yun-Ping Hu,
Lin Jiang,
Zhu-Jun Tan,
Wei Lu,
Ping Wang,
Ying-Bin Liu
Affiliations
Xu-An Wang
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Shan-Shan Xiang
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Huai-Feng Li
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Xiang-Song Wu
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Mao-Lan Li
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Yi-Jun Shu
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Fei Zhang
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Yang Cao
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Yuan-Yuan Ye
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Run-Fa Bao
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Hao Weng
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Wen-Guang Wu
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Jia-Sheng Mu
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Yun-Ping Hu
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Lin Jiang
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Zhu-Jun Tan
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Wei Lu
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Ping Wang
Department of General Surgery, Hangzhou People's First Hospital, No. 261 Huansha Road, Hangzhou 310009, China
Ying-Bin Liu
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Gallbladder cancer is the most common malignant tumor of the biliary tract, and this condition has a rather dismal prognosis, with an extremely low five-year survival rate. To improve the outcome of unresectable and recurrent gallbladder cancer, it is necessary to develop new effective treatments and drugs. The purpose of the present study was to evaluate the effects of cordycepin on human gallbladder cells and uncover the molecular mechanisms responsible for these effects. The Cell Counting Kit-8 (CCK-8) and colony formation assays revealed that cordycepin affected the viability and proliferation of human gallbladder cancer cells in a dose- and time-dependent manner. Flow cytometric analysis showed that cordycepin induced S phase arrest in human gallbladder cancer cell lines(NOZ and GBC-SD cells). Cordycepin-induced apoptosis was observed using an Annexin V/propidium iodide (PI) double-staining assay, and the mitochondrial membrane potential (ΔΨm) decreased in a dose-dependent manner. Additionally, western blot analysis revealed the upregulation of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP and Bax and the downregulation of Bcl-2, cyclin A and Cdk-2 in cordycepin-treated cells. Moreover, cordycepin inhibited tumor growth in nude mice bearing NOZ tumors. Our results indicate that this drug may represent an effective treatment for gallbladder carcinoma.
