Effects of cetuximab on chemosensitivity and radiosensitivity of docetaxel resistant human lung adenocarcinoma cell line SPC-A-1/docetaxel

Abstract

22193 Background: Cetuximab (C225), an anti-epidermal growth factor monoclonal antibody has been used in treatment of advanced head-neck cancer, metastatic colorectal cancer. The effect of C225 on human lung adenocarcinoma cell resistant to chemotherapy is to be elucidated. In the present study, we investigate the modulating effects of C225 on the chemosensitivity and radiosensiticity in a docetaxel resistant human lung adenocarcinoma cell line SPC-A-1/docetaxel. Methods: Radiosensitivity was determined by clone formation experiment and quantified by calculating the enhancement ratio (ER). The growth inhibition of SPC-A-1/docetaxel cell line caused by C225 or combination of C225 and docetaxel in different sequence was detected by MTT assays. The effects on cell cycle distribution and apoptosis caused by C225 alone were determined by flow cytometry. Results: Immunohistochemistry showed a high level of EGFR expression in SPC-A-1/docetaxel cell line. C225 plus radiation significantly decreased the number of the cell clones than radiation alone. D0 calculated from the dose-response curve for radiation combined with C225 and radiation alone were 1.73 Gy and 2.39 Gy respectively. The enhancement ratio was 1.38. C225 alone at concentrations up to 1000 μg/ml for 48 hours had neither cytotoxic nor cytostatic effect to SPC-A-1/docetaxel in vitro. C225 administration followed by docetaxel significant decreased the IC50 of docetaxel. Flow cytometry demonstrated that C225 exposure could induce apoptosis in a time-dependent manner in SPC-A-1/docetaxel. The cell had an increase in the G0/G1 fraction from 43.80±4.46% to 60.50±6.57% after a 24-hour C225 exposure. Conclusions: C225 could enhance the radiosensitivity and chemosensitivity of the docetaxel resistant lung adenocarcinoma cell line SPC-A-1/docetacel, which may be associated with apoptosis induction and cell cycle arrest. No significant financial relationships to disclose.