NCl-H157 폐암 세포주에서 Caspase Cascade 활성을 통한 Arsenic Trioxide와 Sulindac 병합요법의 세포고사 효과 = Inducing Apoptosis of NCl-H157 Humman Lung Carcinoma Cells via Activation of Caspase Cascade by Combination Treatment with ArsenicTrioxide and Sulindac

다국어 초록 (Multilingual Abstract)

Arsenic trioxide(As2O3) was introduced into the treatment of refractory or relapsed acute promyelocytic leukemia. Some investigators have reported that arsenic trioxide had induced apoptosis in a variety of solid human tumor cell lines, including non-small cell lung cancer. Non-steroidal anti-inflammatory drugs(NSAIDs) are powerful chemopreventive agents for gastrointestinal cancers and the growth of established tumors are reduced by inducing apoptosis. It's also reported that NSAIDs enhanced tumor response to chemotherapeutic drugs or radiation. In this study, we aimed to determine whether combination of arsenic trioxide with sulindac augmented its apoptotic potential in NCI-H157 human lung cancer cells. The human lung cancer cell line NCI-H157 was treated with arsenic trioxide and sulindac. Cell viability was measured by the MTT assay. Apoptosis was measured by nuclear staining and flow cytometric analysis. The catalytic activity of the caspase families were measured by the fluorogenic cleavage of biosubstrates. The western blotting were also performed to define the mechanical basis of apoptosis.Combination treatment of arsenic trioxide and sulindac decreased the viability of NCI-H157 human lung cancer cells in a dose-dependent manner. The catalytic activity of caspase-3, 8 and 9 proteases were increased after combination treatment. Consistently PARP was cleaved from 116kDa to 85kDa fragments, and the expression of ICAD was decreased by time-dependent manner. Also combination treatment increased the expression of Fas and Fas/L.Combination therapy of arsenic trioxide with sulindac augments cell death and induces apoptosis via the activation of caspase cascade in NCI-H157 human lung carcinoma cells.(Tuberculosis and Respiratory Diseases 2004, 56:381-392)

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