Investigation of the hypoxia activated epidermal growth factor receptor and signal transduction pathway in head and neck squamouse cell lines

• Main Authors: Su Chih-Sheng, 蘇志勝
• Other Authors: Kang Bor-Hwang
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/65889880798684712044

碩士 === 國防醫學院 === 海底醫學研究所 === 97 === 　Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of human cancer in the world. In Taiwan, HNSCC is one of the ten leading causes of cancer death. According to Health and Vital Statistics Republic of China in 2007, oral cancer is the fourth leading cause of cancer death in man. The mortality rate of oral cancer was 10.1 per 100,000 and gradually increasing. Epidemiological studies have indicated that the cigarette smoking, alcohol drinking and betel quid chewing are the major risk factors of oral cancer in Taiwan. However, the molecular genetic alterations underlying its malignant behavior and progression are little known. High levels of epidermal growth factor receptor（EGFR）expression are correlated with poor prognosis and resistance to chemoradiation therapy in a variety of cancers, mostly in HNSCC. The expression of EGFR of head and neck cancer is very high up to 80-100%. Otherwise, many studies have described the rapidly growing progression of tumor incurring hypoxia that would be close to the necrotic areas in tumors. Under certain hypoxic condition, Cellular adaptation to hypoxia is largely driven by hypoxia-induced alterations in gene transcription, mRNA translation and protein stability. Previous studies have showed that hypoxia can activate epidermal growth factor receptor and induce cancer cell angiogenesis, invasiveness, treatment resistance and overall poor clinical outcome. Therefore, we investigate hypoxia activate EGFR signal transduction pathway, cell proliferation and cell invasion in HNSCC. We studied the effects of hypoxia in the FADU and SCC25 cell line cultured in less 1% O2 for different time period. The expression of the activated EGFR, p-AKT and p-ERK were evaluated by using the Western blot analyses. Then, the effects of head and neck squamouse cell lines on cell invasion were observed by transwell Cell Invasion Matrigel Assay. Finally, we used trypan blue exclusion assay, BrdU assay and MTT assay for detecting cell proliferation. We found that hypoxia cause the induction of activated EGFR and the downstream signal transduction pathway. Hypoxia also induce invasive behavior of FADU cell. LY294002 (PI3K inhibitor) and U0126 (MEK inhibitor) blocked cell proliferation and cell invasive behavior induced by hypoxia. These findings supported that hypoxia might play an important role in tumor cell invasion. Therefore, our study demonstrate hypoxia may affect the cell invasion of HNSCC by EGFR and the downstream signal transduction pathway.