Establishment of orthotopic oral cancer models and evaluation of the inhibition effects of deguelin on tumor metastasis

• Main Authors: Po-Sheng Huang, 黃柏盛
• Other Authors: Yen-Ping Kuo
• Format: Others
• Language: en_US
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/08396335961656226307

碩士 === 國立臺灣大學 === 口腔生物科學研究所 === 96 === In Taiwan, oral cancer is the sixth leading cause of cancer-related death in year 2006, and it is the fifth leading cause of cancer-related deaths in male population on this island. The disease causes great morbidity, and the five-year survival rate of less than 50 % has not improved in more than two decades. Squamous cell carcinoma (SCC) is the most frequently a occurred cancer in the oral and maxillofacial regions, and its metastatic and invasive abilities tendencies made it difficult in prognostic control. In our study, we determined infection efficiencies in seven oral cancer cell lines and oral mucosa fibroblast (OMF) with different lentivirus dosage. The results suggested that using lentivirus for gene delivery is a promising method. We used 20 MOI GL-lentivirus to infect Ca922 and SAS cell lines to establish stable cell lines with GL expression. The Ca922-GL and SAS-GL orthotopic tumor models were established by these two stable cell lines. Based on bioluminescent imaging observation, SAS was highly invasive cell line, while Ca922-GL was not an invasive cell line in vivo. In SAS-GL orthotopic model, a metastatic tumor was observed on salivary gland. However, in Ca922-GL orthotopic model, no metastatic tumor was found in mice at all. Deguelin is a natural product and an AKT inhibitor. In cell viability assay, Ca922, Cal27, and SAS were sensitive to deguelin. To determine the inhibition efficacy of deguelin treatment on tumor growth, we used SAS-GL orthotopic tumor model with 0.8 mg/kg and 4 mg/kg deguelin treatment. In 4 mg/kg deguelin treatment, the tumor volume in SAS-GL orthotopic tumor model was significantly smaller than the control group. In addition, treatment with 0.8 mg/kg deguelin in SAS-GL orthotopic tumor model also resulted in a smaller tumor. Overall, our results indicated that the tumor growth of oral cancer could be inhibited by deguelin treatment, and this novel strategy may provide an additional treatment for OSCC