Characterization of cisplatin-resistant squamous cell carcinoma cell lines

Autor: Hsing-Han Lu, 盧星翰
Rok vydání: 2014
Druh dokumentu: 學位論文 ; thesis
Popis: 102
Cisplatin is used in the treatment of cancer for over 30 years. It is one of the most effective anti-cancer regimens for testicular cancer, ovarian, cervical, head and neck, small cell lung cancers. Cisplatin can also be combined with other anti-cancer drugs to treat cancer. However, the efficacy of cisplatin-based therapy is declined due to drug resistance. This study evaluates the role of DNA repair in cisplatin resistance by comparing the DNA repair capacity and gene expression between the cisplatin-resistant HB8 cells and the parental HEp-2 cells. The sensitivities of HB8 and HEp-2 to cisplatin, KU55933, and olaparib, two inhibitors that can modulate DNA repair were examined by MTT assays. The results showed that HB8 exhibited elevated DNA repair activities in nucleotide excision repair (NER), homologous recombination repair (HRR), and non-homologous end-joining (NHEJ) repair when compared with HEp-2 cells. The expressions of DNA repair genes in HB8 cells are higher than those in HEp-2 cells as well. In addition, caspase activity is upregulated by KU55933, either treatment alone or in combination with cisplatin. Taken together, these results suggest that (1) cisplatin resistance is correlated with the increase of NER, HRR and NHEJ; (2) KU55933 may be beneficial to improve treatment of cisplatin-resistant cancers.
Databáze: Networked Digital Library of Theses & Dissertations