Identification of radioresistant genes in oral cancer cells

• Main Authors: Lin,Ting-Yang, 林庭揚
• Other Authors: Cheng, Ann-Joy
• Format: Others
• Language: en_US
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/79398808153315857668

碩士 === 長庚大學 === 醫學生物技術研究所 === 95 === Abstract In Taiwan, the incidence of oral cancer has become the 6th leading cancer, and is still increasing in recent years. Since oral cancer usually occurs in the middle age male, at the high peak of life responsibility, it has tremendous impact on family and society. Radiation therapy is an integral part of the treatment of oral cancer. However, local recurrence or tumor persistence after radiation therapy, that is radioresistant (RR) of the cancer, is the major cause of treatment failure. To investigate radioresistant mechanism, we established radioresistant (RR) subclones of two oral cancer cell lines, OEC-M1 and KB. After characterization of the radioresistant phenotype, the differential proteomes of parental and RR subclones were analyzed by gradient gel electrophoresis and identified by Mass spectrometry. Seven genes were identified as candidate RR genes. Gp96, Enolase-1 and annexin A2 were identified up-regulated in RR subclones. Heat shock protein Gp96 and TGF-ß family protein GDF-15 were previously examined up-regulated in Nasopharyngeal cancer RR subclones. We investigate the role of Gp96 and GDF-15 in the radioresistance of oral cancer. gp96 and GDF-15-siRNA were constructed and transfected into oral cancer cells to examine alterations of their radiosensitivity. Prolonged radiation-induced growth delay, reduced colongenic survival, G2-M phase cell cycle arrest and enhanced ROS level were found in the gp96-siRNA transfectants. In vivo xenograft model further demonstrates that Gp96 RNAi can serve as a radio-sensitizer for oral cancer treatment. These results demonstrate that Gp96 is involved in the radioresistant mechanisms of oral cancer. Knockdown of Gp96 may enhance radiosensitivity, which may lead to better prognosis in oral cancer treatment.