Abstract
Gallbladder cancer, with high aggressivity and extremely poor prognosis, is the most common malignancy of the bile duct. The main objective of the paper was to investigate the effects of schisandrin B (Sch B) on gallbladder cancer cells and identify the mechanisms underlying its potential anticancer effects. We showed that Sch B inhibited the viability and proliferation of human gallbladder cancer cells in a dose-, time -dependent manner through MTT and colony formation assays, and decrease mitochondrial membrane potential (ΔΨm) at a dose-dependent manner through flow cytometry. Flow cytometry assays also revealed G0/G1 phase arrest and apoptosis in GBC-SD and NOZ cells. Western blot analysis of Sch B-treated cells revealed the upregulation of Bax, cleaved caspase-9, cleaved caspase-3, cleaved PARP and downregulation of Bcl-2, NF-κB, cyclin D1 and CDK-4. Moreover, this drug also inhibited the tumor growth in nude mice carrying subcutaneous NOZ tumor xenografts. These data demonstrated that Sch B induced apoptosis in gallbladder cancer cells by regulating apoptosis-related protein expression, and suggests that Sch B may be a promising drug for the treatment of gallbladder cancer.
Highlights
Gallbladder cancer, the most common malignancy of the bile duct, is an extremely aggressive, lethal neoplasm [1,2,3,4,5,6]
To test the effect of schisandrin B (Sch B) on the proliferation of gallbladder cancer cells, GBC-SD and NOZ cells were treated with various concentrations (0, 20, 40, 60, 80 and 100 μmol/L for both cells) of Sch B for
The findings indicate that Sch B may exert a significant influence on GBC-SD and NOZ cell viability and proliferation
Summary
Gallbladder cancer, the most common malignancy of the bile duct, is an extremely aggressive, lethal neoplasm [1,2,3,4,5,6]. Curative resection remains the only effective treatment for gallbladder cancer, the majority of the patients will have frequent recurrences after surgery. For unresectable and recurrence patients, chemotherapy or radiotherapy will be the only treatment, but it does not have satisfactory results [8,9]. Novel effective drugs are urgently needed in order to improve the outcome of patients with advanced gallbladder cancer. Sch B on gallbladder cancer cells and the underlying mechanisms have not been reported previously. We investigated the anti-neoplastic activity of Sch B in gallbladder cancer cell lines (including GBC-SD and NOZ cell lines) in vitro and in vivo, and explored the possible molecular mechanisms underlying this action, which could provide experimental evidence for the potential application of Sch B as a new natural anti-tumor medicine for gallbladder cancer
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