Inhibition of ICAM2 induces radiosensitisation in oral squamous cell carcinoma cells
Inhibition of ICAM2 induces radiosensitisation in oral squamous cell carcinoma cells
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DOI：
10.1038/sj.bjc.6604290
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发表时间：
2008-04-22
影响因子：
8.8
通讯作者：
Tanzawa, H.
中科院分区：
文献类型：
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作者：
Ishigami, T.;Uzawa, K.;Tanzawa, H.
最近，我们使用Affyssin基因芯片鉴定了与口腔鳞状细胞癌（OSCC）放射抵抗相关的基因和分子通路。本研究旨在探讨靶基因之一细胞间粘附分子2（ICAM 2）与口腔鳞癌细胞对X射线照射的耐受性之间的关系，并评价ICAM 2小干扰RNA（siRNA）联合X射线照射的抗肿瘤效果。通过siRNA下调ICAM 2表达增强了OSCC细胞的放射敏感性，通过AKT的磷酸化（ser 473）和caspase-3的活化增加了凋亡表型。此外，ICAM 2的过度表达诱导了具有放射抵抗表型的OSCC细胞对X射线照射的更大抵抗。提示ICAM 2的沉默与口腔鳞癌细胞对放射治疗的敏感性密切相关，ICAM 2可能是口腔鳞癌有效的放射治疗靶点。
We recently identified genes and molecular pathways related to radioresistance of oral squamous cell carcinoma (OSCC) using Affymetrix GeneChip. The current study focused on the association between one of the target genes, intercellular adhesion molecule 2 (ICAM2), and resistance to X-ray irradiation in OSCC cells, and evaluated the antitumor efficacy of combining ICAM2 small interfering RNA (siRNA) and X-ray irradiation. Downregulation of ICAM2 expression by siRNA enhanced radiosensitivity of OSCC cells with the increased apoptotic phenotype via phosphorylation (ser473) of AKT and activation of caspase-3. Moreover, overexpression of ICAM2 induced greater OSCC cell resistance to the X- ray irradiation with the radioresistance phenotype. These results suggested that ICAM2 silencing is closely related to sensitivity of OSCC cells to radiotherapy, and that ICAM2 may be an effective radiotherapeutic target for this disease.