The role of hepatocyte growth factor activator inhibitor-2 in response to cisplatin treatment in oral squamous cell carcinoma

• Main Authors: Shang-Yi Chiu, 邱尚儀
• Other Authors: Kan-Tai Hsia
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/34719554171047087787

碩士 === 國立陽明大學 === 口腔生物研究所 === 102 === Hepatocyte growth factor activator inhibitor type 2 (HAI-2) is one of the Kunitz-type serine protease inhibitor. The function of HAI-2 is to inactivate the serine protease and the downstream signaling transduction. The previous study found that the HAI-2 expression was usually down-regulated in many cancers and the downstream receptor tyrosine kinase, such as c-Met. Cisplatin is one of the commonly used anti-cancer drugs. It could form DNA adduct and induce cancer cells apoptosis. But the role of HAI-2 expression in OSCC under cisplatin treatment is unknown. We found that HAI-2 expression was significantly associated with the primary tumor stage in OSCC patients. To figure out the role of HAI-2 in oral squamous cell carcinoma (OSCC), we established HAI-2 knock-down and HAI-2 overexpressed cancer cell lines. The data showed that the cell growth and migration abilities were up-regulated in HAI-2 knockdown cell lines and were down-regulated in HAI-2 overexpression cell line. On the other hand, the cytotoxicity was promoted in HAI-2 knockdown cell lines under cisplatin treatment. The data revealed that the apoptosis trigger by cisplatin in HAI-2 knockdown cells was lower than scramble cell lines. Western blot analysis showed that the level of matriptase-2, phosphorylated c-Met and phosphorylated Akt were increased and cleaved caspase 3 and 9 were decreased in HAI-2 knockdown cell lines under cisplatin treatment. In conclusion, we suggest that HAI-2 might suppress the tumorigenesis and low expression of HAI-2 could inhibit the apoptosis triggered by cisplatin in OSCC.