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Expression and translocation of targeted antigen of anti-lung cancer 15A1 monoclonal antibody in lung cancer cells
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Abstract:
Objective:To study the expression, subcellular localization and translocation of the targeted antigen of anti-lung cancer 15A1 mAb in lung cancer cells, and to study the inhibitory function of 15A1 mAb in vitro and in vivo against lung cancer cells, so as to provide target and antibody drug candidate for targeted therapy of lung cancer. Methods: The expression and localization of the targeted antigen of 15A1 mAb in lung cancer cell lines and lung cancer tissues were studied by immunofluorescence and flow cytometry. CCK-8 proliferation assay and tumor xenograft experiment were performed to evaluate the inhibitory function of 15A1 mAb aginst lung cancer cells in vitro and in vivo. Results:The antigen of 15A1 mAb was expressed in the cytoplasm and cell surface of 12 lung cancer cell lines, including human lung adenocarcinoma cell lines (A549, ANIP-793, GLC-82, Calu-3, H157, H1299), squamous carcinoma cell lines (GLC-P, H520), small cell lung cancer cell lines (H446, H209), and large cell lung cancer cell lines (PG, H460), with the highest expression level seen in the adenocarcinoma cell lines. The upregulated expression of the targeted antigen of 15A1 mAb was found in about 75% of human lung cancer tissues. Most targeted antigen translocated from the nucleus to cytoplasm in lung adenocarcinoma cells, but only part of the antigen translocated to the cytoplasm in lung squamous carcinoma cells. Some antigen also translocated to the cell membrane, which was more significantly in adenocarcinoma cells than in squamous carcinoma cells. The 15A1mAb greatly suppressed proliferation of lung cancer cells in vivo and in vitro, with the inhibitory rate being 25%〖KG-*2〗〖DK〗-80%. Conclusion: The 15A1 mAb can significantly inhibit growth of lung cancer cells in vivo and in vitro, and its targeted antigen is highly expressed on human lung cancer tissues and cells and can translocate to the cell surface, suggesting that 15A1 mAb might become a candidate target for lung cancer therapy.
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Project Supported:
Supported by the National Basic Research Program of China (No.2009CB521804) and the National S & T Major Project (No.2009ZX09401-005 and 2009ZX09103-713)
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