Oncoprotein 18 overexpression Increases the sensitivity to vindesine in the Human hung Carcinoma Cells

BACKGROUND. Oncoprotein 18 (op18) was first isolated as a molecule overexpr essed in several malignant cells, suggesting a function of op18 in malignan t processes, such as differentiation in hematologic malignancies, op18 also was found to enhance microtubule deassembly in the cells. Antimitotic agen ts that bind to tubulin have been used for chemotherapy to treat solid tumo rs, such as lung carcinoma. Vinca alkaloids, such as vindesine and vincrist ine, have commonly been used for chemotherapy of nonsmall cell lung carcino ma. The authors examined the role of op18 in the sensitivity of human lung carcinoma cells to antimitotic agents. METHODS, Expression of op18 mRNA was detected in all 17 lung carcinoma cell lines tested by Northern blotting. Oncoprotein 18 cDNA was transfected to SBC-3 human lung carcinoma cells, and the stable transfectants, SBC-3/op1-3 , were isolated. The sensitivity of these transfectants against antimitotic agents were examined by the MTT assay in vitro. Cell cycle distribution of the transfectants on DNA histogram was analyzed by flow cytometry. RESULTS. Oncoprotein 18-transfected cells showed higher sensitivity to vind esine and vincristine, but not to taxanes. Vindesine-exposure increased the G2/M population of the cell cycle in the Mock transfectants, but not in SB C-3/op1, suggesting that the cell cycle dynamics were altered by op18 expre ssion in SBC-3/op1. CONCLUSION, Oncoprotein 18 expression is associated with lung carcinoma cel l sensitivity to vindesine and may be able to serve as a surrogate marker f or the chemosensitivity to Vinca alkaloids in human lung carcinomas. Cancer 2001;91: 1494-9. (C) 2001 American Cancer Society.