Reverse resistance to radiation in KYSE-150R esophageal carcinoma cell after epidermal growth factor receptor signal pathway inhibition by cetuximab

Background and purpose: The purpose of our study is to examine the capacity of cetuximab to teverse radiation resistance and investigate molecular mechanisms in human radiation-resistant esophageal carcinoma cell line KYSE-1508 Materials find methods: The radioresistant cell line KYSE-1508 was established by using fractionated irradiation (FIR). - The KYSE-1508 cell line was exposed to radiation, treatment with cetuximab, and combined treatment. Cell cycle distribution and apoptosis were analyzed using flow cytometry Radiation Survival was analyzed using clonogenic assays. RT2 profiler(III) PCR array was performed to analyae EGF/PDGF signaling pathway genes Results: The established esophageal carcinoma cell line KYSC-1508 showed higher radroresrstance than parental cell line. Cetuximab could reverse the radiation resistance of KYSE-1508 cells. Cell cycle analysis showed that combination with radiation and cetuxlmab resulted in the accumulation of cells in G1 and G2/M phases, with the reduction of cells within the S phase Cetuximab enhanced the apoptosis induced by radiation. RV profiler(B3) array showed that some intracellular signaling genes deriving from EGF/PDGF signaling pathway regulated by cetuximab. Conclusions Irradiation combined with EGFR blocked by cetuximab may reverse the resistance to radiation in radioresistant esophageal carcinoma cell, hlte mechanisms may include cell cycle perturbation and enhancement of radiation-induced apoptosis. Further studies are needed to evaluate the role of cetuximab in combination with radiotherapy in the management of esophageal carcinoma (C) 2009 Elsevier Ireland Ltd. All rights reserved Radiotherapy and Oncology 93 (2009) 468-473