Abstract
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.
Highlights
Gallbladder cancer, an aggressive and highly lethal malignancy, is the most frequent cancer of the biliary tract and the most common neoplasm of the digestive system [1,2,3,4,5]
398.1 μg/mL, respectively, which indicates that cordycepin could inhibit the proliferation capability of gallbladder cancer cells
We investigated the effect of cordycepin on the proliferation of gallbladder cancer cells using a colony assay
Summary
Gallbladder cancer, an aggressive and highly lethal malignancy, is the most frequent cancer of the biliary tract and the most common neoplasm of the digestive system [1,2,3,4,5]. Complete resection is the primary curative treatment for gallbladder cancer; more than half of gallbladder cancer patients have unresectable tumors at diagnosis, and recurrence after surgery is common. Palliative therapy, such as chemotherapy and radiotherapy, are often introduced to improve prognosis; these treatments are often ineffective [8,9]. Cordycepin (3'-deoxyadenosine) (Figure 1), a chief ingredient and the active component of Cordyceps sinensis, is widely used in traditional Chinese medicine [10,11] This drug is a derivative of the nucleoside, adenosine, but lacks an oxygen in the 3' position of its ribose moiety, which results in the termination of chain elongation during RNA synthesis. 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
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