Experimental Study Of Docetaxel Synchronous Radiation Treatment Of Non-small Cell Lung Cancer

Part 1: The effect of docetaxel as a radiosensitizer on the SPC-A1 lung cancer cells in vitroOBJECTIVE: The aim of this study was to determine the radiosensitizing effect of docetaxel on SPC-A1 lung cancer cell line, and its radiosensitizing mechanism on the aspect of reactive oxygen species (ROS).METHODS: SPC-A1 lung cancer cells were exposed to 1.25×10-10 mol/L and 2.5×10-10 mol/L of docetaxel for 24 or 48 hours respectively preirradiation. After incubated in the docetaxel, the cells were irradiated with 137Cs γ-rays radiator at single fraction from 2 to 10 Gy. For each radiation dose, the docetaxel-treated cells and the non-treated cells were irradiated simultaneously. Dose-response curves for radiation alone, and "corrected" docetaxel plus radiation were produced by plotting the means of triplicate determinations of colony-forming assay. The curves were regressed according to single target multihit model. The "corrected" docetaxel plus radiation dose-response curve was created by dividing the observed docetaxel plus radiation SF by the SF observed for docetaxel alone. The sensitivity enhancement ratio (SER) were calculated from the normalized survival curves at the 37% survival level using the SigmaPlot software program. To explore the docetaxel radiosensitizing mechanism, SPC-A1 lung cancer cells were treated with 1.25×10-10 mol/L and 2.5×10-10 mol/L of docetaxel for 24 or 48 hours to estimate the ROS levels by staining with 2',7'－dichlorofluorescin diacetate and dihydroethidine by flow cytometry. RESULTS: The radiosensitizing effect of docetaxel on SPC-A1 lung cancer cells was observed in this experiment. The SER at 37% survival level were 1.10 and 1.36 for 24 and 48 hours pretreatment of docetaxel at the dose of 1.25×10-10 mol/L, while it were 1.23 and 1.43 at the dose of 2.5×10-10 mol/L for 24 and 48 hours pretreatment, respectively. Intracellular levels of ROS at experimental groups were statistically higher than control group after student t test (P<0.05).CONCLUSION: This study, focused on the assessment of the interaction between chemotherapeutic agent docetaxel and radiation treatments in SPC-A1 lung cancer line, demonstrated that docetaxel is synergistic with radiotherapy to lung cancer cell in vitro. We speculate that ROS might be involved in the process docetaxel-induced radiosensitization. ROS may play a substantial role.KEY WORDS: docetaxel;SPC-A1 lung cancer cell;radiosensitization;reactive oxygen species...