Effect of atractylodin compound inhibition on cholangiocarcinoma cells proliferation, migration, invasion, and apoptosis

抄録

Cholangiocarcinoma (CCA) is an important cancer in the Great Mekong region, particularly in Thailand. High incidence of CCA is reported from the northeastern Thailand, where the liver fluke Opisthorchis viverrini is endemic and that is the major cause of CCA. Limitation of treatment option and the lack of effective diagnostic tool for early detection of CCA are of major concerns for the control of this type of cancer nowadays. The aim of the study was to investigate cytotoxic, antioxidant, apoptotic and inhibitory activities on cell migration and cell invasion of atractylodin, the active constituent of Atractylodes lancea (Thunb.) DC. against CCA cell line CL-6. The fibroblast cell (OUMS) was used as normal control cell line. MTT assay was used to test cytotoxicity. DPPH scavenging activity was used to test antioxidant effect. CellEvent™ Caspase-3/7 Green Detection Reagent was specific test to analyze activity on cell apoptosis and xCELLigence Real-Time Cell Analyzer (RTCA) DP system was used to test cell migration and invasion. The concentration that inhibits cell growth to 50% (IC50) [median (range) values] for atractylodin in CL-6 and OUMS were 40.03 (39.88-42.39) and 101.74 (99.75-110.42) µg/ml, respectively, with selectivity index of 2.09. The corresponding values for the reference drug 5-fluorouracil (5-FU) were 43.92 (89.74-96.33) and 92.15 (87.48-97.71) µg/ml, respectively, with selectivity index of 2.54. The atractylodin compound also exhibited inhibitory activity on cell migration and cell invasion with the concentration of 20, 40 and 80 µg/ml. In addition, it induced cell apoptosis. These findings may provide the potential role of atractylodin compound for further development a new approach as chemotherapeutic for CCA.