Effects Of Erlotinib Combined With X-ray Radiation On Growth Of The Esophageal Carcinoma Cells KYSE450

Objective:To study the radiation-sensitizing effects of erlotinib and X-ray radiotherapy on human esophageal carcinoma KYSE450 cells.Methods:Human esophageal carcinoma cells KYSE450 were respectively treated with erlotinib, irradiation and both. The cell growth inhibition was evaluated by MTT assay. Cell cycle distribution and apoptosis were analyzed by flow cytometry assay.Cell radiosensitivity was tested by clonogenic assay and the survival curve was fitted with the multi—targets single-hit model. Combination group and accelerated radiation group were tested by microarray technology and then screened the differentially expressed genes among two groups.Results:The growth of KYSE450 cells has been inhibited in all the 3 groups, namely the group with erlotinib treatment, the group with irradiation treatment and the group with both. The inhibition was found gradually increased with the increasing of the concentration of erlotinib in the range of 5 ug/mL ~150 ug/mL. Moreover, greater inhibition rate(21.45%) was found in the group of erlotinib combined with irradiation,which is a significant difference compared with the erlotinib group(13.81%) and irradiation group(16.84%)(F=15.147,P <0.001). Obvious G2 phase arrest and cell apoptosis appeared in the group of erlotinib combined with irradiation. Erlotinib and irradiation had interaction in G2 phase arrest(F=32.921,P <0.001), but not obvious in cell apoptosis(F=1.123,P=0.052). It has been revealed by applying the multi-targets single-hit model that the values of Dq and D0 in the group with both treatments weresmaller than those of the irradiation group, with the sensitization enhancement ratio(SER) being 1.52, which indicated the radiosensitization effect of erlotinib on KYSE450 cells.Conclusions:This experiment shows that erlotinib can effectively inhibit the growth of human esophageal cancer cell KYSE450. It can also promote apoptosis and G2 phase arrest when combined with X-ray radiotherapy, thus enhancing the radiosensitivity of KYSE450 cells.