Evaluation of caspase-3 overexpression as a chemosensitizer in tumor gene therapy

• Main Author: 張鈺偵
• Other Authors: 鄭謙仁
• Format: Others
• Language: en_US
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/24152643749845235263

碩士 === 國立臺灣大學 === 獸醫學研究所 === 90 === Abstract Abnormality in apoptosis is deeply involved in oncogenesis and the malignant progression of cancers. To trigger the tumor cells undergo apoptosis is the aim of most tumor treatment. Today, the most chemotherapeutic agents kill tumor cells by triggering them to go to apoptosis. But there is obstacle to tumor chemotherapy; many tumors are resistant to antitumor drug. Since apoptosis is executed by a set of genes; caspases family, we want to investigate whether overexpression of caspase-3 (the central role of apoptosis signal transduction) can increase chemosensitivity in tumor. In our study, caspase-3 overexpression in 293 cell which have normal gene function has no obvious effect to cisplatin treatment, and in the tumor model, we established the caspase-3 overexpressed stable clone to evaluate caspase-3 as a chemosensitizer. But the results are unexpected, the possibility may be that cells are tightly regulated in growth and apoptosis to maintain homeostasis. There are a set of complex genes involved in. As our findings in the two casapse-3 overexpressed clones, they underwent G2/M arrest rather than apoptosis. The p53 and p21 may play a role in this situation. And whether our manipulation induce the intrinsic antiapoptotic gene overexpression to neutralizing the overexpressed caspase-3 still to be investigate. In brief, we have successfully establish caspase-3 overexpressed HeLa stable clones for chemosensitivity assay, but the effect of caspase-3 overexpression caused a controversial results. That may due to the influence of antiapoptotic and cell regulator proteins status in cells.