Author Description

This dissertation, "Novel Role of Drug-induced Non Homologous End Joining Factor 1 in the Chemoresistance of Hepatocellular Carcinoma" by Sitian, Yang,, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Hepatocellular carcinoma (HCC) is highly resistant to chemotherapy and one of the most common causes of cancer related death worldwide. Chemoresistance in HCC leads to restricted treatment option and poor prognosis. Acquired cellular chemoresistance mechanisms include oncogenes mutation, multi-drug resistance gene (MDR1) over expression or hypermethylation, cancer stem cells enrichment, and dysfunctional apoptosis. Most cytotoxic drugs serve as DNA damaging agents and are able to generate various DNA damages among which double strand breaks (DSBs) are the most toxic. Cellular responses such as increased DNA damage repair might imply a potential chemoresistance, which is not well defined in HCC. In this project, I aim to identify potential role of NHEJ1 mediated non homologous end joining (NHEJ) repair in HCC chemoresistance. Chemo-drugs with diverse damaging effects (cisplatin/oxaliplatin: bulky adducts and cross link; doxorubicin: single strand breaks; 5-Fu: mismatch bases) can induce DSBs in HCC cells. In response, expressions of the key genes involved in NHEJ pathway were significantly increased. By calculating chemo-drugs IC50 concentration, we found that IC50 of HCC line 97L was significantly higher than PLC cells. Using the plasmid-based cell-free and live cell NHEJ assay, 97L cells displayed significantly enhanced NHEJ activity in both in vitro and in vivo assay, whereas PLC cell did not show drug