Ming Bai1, Wei Li2, Nanze Yu1, Hailin Zhang1, Fei Long1, Ang Zeng1. 1. Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeBeijing 100730, China. 2. Center of Interventional Oncology and Liver Diseases, Beijing You'an Hospital, Capital Medical UniversityBeijing 100069, China.
Abstract
BACKGROUND/ OBJECTIVE: IFNs induce potent antiviral and antitumor activities. β-catenin pathway is a surviving pathway adapted by carcinogenetic mechanisms of various cancers. Crosstalk between these pathways has not been well described in lung cancer cells. METHODS: Lung cancer cell lines, A549 and Calu-3, were used in this study. β-catenin protein levels and signaling activities were tested by flow cytometry and luciferase assay. Cell proliferation was measured by counting viable cells under microscope, and apoptosis by TUNEL assay and caspase 3 activation. DKK1 and GSK3β levels were tested by flow cytometry. Secreted DKK1 was measured by ELISA. αDKK1 , FLUD and S3I were to inhibit DKK1, STAT1 and STAT3 activities, respectively. RESULTS: All of IFNα, IFNγ and IFNλ1 suppressed β-catenin signaling in A549 and Calu-3 cells, where IFNγ was the strongest (P<0.05). They inhibited cellular proliferation and promoted apoptosis. IFNγ gave greater induction ability compared to IFNα and IFNλ1 (P<0.05). All tested IFNs promoted DKK1 activation but not GSK3β in A549 and Calu-3 cells. IFNs activated STAT1 and STAT3. But only STAT3 was vital for IFN-mediated DKK1 activation and apoptosis. Plus, DKK1 antagonist abrogated IFN-mediated apoptosis. The degree of STAT3 activation was corresponding to the level of apoptosis induced by different IFNs (P<0.05). CONCLUSIONS: In lung cancer cells, all three types of IFNs can induce apoptosis via suppressing β-catenin signaling by a STAT3- and DKK1-dependent manner. This findings demonstrate a link between IFNs and β-catenin signaling, which may possess potentials on the development of novel therapeutic measures against lung cancer.
BACKGROUND/ OBJECTIVE: IFNs induce potent antiviral and antitumor activities. β-catenin pathway is a surviving pathway adapted by carcinogenetic mechanisms of various cancers. Crosstalk between these pathways has not been well described in lung cancer cells. METHODS:Lung cancer cell lines, A549 and Calu-3, were used in this study. β-catenin protein levels and signaling activities were tested by flow cytometry and luciferase assay. Cell proliferation was measured by counting viable cells under microscope, and apoptosis by TUNEL assay and caspase 3 activation. DKK1 and GSK3β levels were tested by flow cytometry. Secreted DKK1 was measured by ELISA. αDKK1 , FLUD and S3I were to inhibit DKK1, STAT1 and STAT3 activities, respectively. RESULTS: All of IFNα, IFNγ and IFNλ1 suppressed β-catenin signaling in A549 and Calu-3 cells, where IFNγ was the strongest (P<0.05). They inhibited cellular proliferation and promoted apoptosis. IFNγ gave greater induction ability compared to IFNα and IFNλ1 (P<0.05). All tested IFNs promoted DKK1 activation but not GSK3β in A549 and Calu-3 cells. IFNs activated STAT1 and STAT3. But only STAT3 was vital for IFN-mediated DKK1 activation and apoptosis. Plus, DKK1 antagonist abrogated IFN-mediated apoptosis. The degree of STAT3 activation was corresponding to the level of apoptosis induced by different IFNs (P<0.05). CONCLUSIONS: In lung cancer cells, all three types of IFNs can induce apoptosis via suppressing β-catenin signaling by a STAT3- and DKK1-dependent manner. This findings demonstrate a link between IFNs and β-catenin signaling, which may possess potentials on the development of novel therapeutic measures against lung cancer.
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