Nimotuzumab enhanced the radio sensitivity of esophageal squamous cell carcinoma / 中国肿瘤临床

ABSTRACT

Objective:To study the radiation-sensitizing effects of nimotuzumab and X-ray radiotherapy on human esophageal carcino-ma KYSE450 cells. Methods:Human esophageal carcinoma cells KYSE450 were treated with nimotuzumab, irradiation, and the combi-nation of both. Cell growth inhibition was evaluated by MTT assay, and cell cycle distribution and apoptosis were analyzed by flow cy-tometry assay. Cell radiosensitivity was tested by clonogenic assay, and the survival curve was fitted using multi-target single-hit mod-el. The combination and accelerated radiation groups were tested by microarray technology, and the differentially expressed genes were screened among the two groups. Results:The growth of KYSE450 cells was inhibited in three groups, namely, the group treated with nimotuzumab, the group treated with irradiation, and the group treated with both. The group treated with both nimotuzumab and irradiation resulted in the highest inhibition rate (35.25%±5.62%) compared with that of the nimotuzumab (16.12%±8.73%) and ir-radiation groups (27.64%± 6.66%) (F=10.953, P<0.001). The highest rates of G2 phase arrest and cell apoptosis were observed in the group treated with the combination of nimotuzumab (29.37%±7.29%) (F=17.299, P<0.001) and irradiation (18.80%±2.03%) (F=85.691, P<0.001). Multi-target single-hit model showed that the values of SF2, Do, and Dq in the group with both treatments were smaller than those of the irradiation group with sensitization enhancement ratio of 1.63, which confirmed the radiosensitization effect of ni-motuzumab on KYSE450 cells. Microarray technology analysis found that nimotuzumab can enhance the radiosensitivity of esophageal squamous cell carcinoma by cutting the genes of EGF/PDGF signaling pathways. Conclusion:This experiment shows that nimotuzumab can effectively inhibit the growth of human esophageal cancer cell KYSE450. Nimotuzumab can also promote apoptosis and G2 phase arrest when combined with X-ray radiotherapy, thereby enhancing the radiosensitivity of KYSE450 cells. This effect is associated with cutting the genes of EGFR signaling pathways.