Investigation of the Combination Anticancer Effects of Olaparib and SAHA in Small Cell Lung Cancer

• Main Authors: Chung, Hui-Yu, 鍾惠伃
• Other Authors: Liang, Mei-Chih
• Format: Others
• Language: en_US
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/aw8zcu

碩士 === 國立交通大學 === 分子醫學與生物工程研究所 === 107 === Lung cancer is the leading cause of cancer deaths. It can be divided into two types, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Among them, SCLC has the characteristics of rapid growth, early metastasis, high aggressive and intensive drug resistance. Thus the mortality rate of SCLC is head and shoulders above NSCLC. Alongside this, there is very limited medical strategies in clinical trial. Therefore, a novel therapeutic approach for SCLC is essential. Olaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor leading to DNA single-strand break unable to repair itself, brings about double-strand break. Existing researches indicate that SAHA, a histone deacetylase (HDAC) inhibitor can disrupt homologous recombination repair by down regulating the expression of BRCA and Rad51. This enhances anticancer efficacy of olaparib. Nevertheless, the combination has not been tested in SCLC. In this study, we tested cell viability, apoptosis, cell-cycle distribution, and signaling molecules with SCLC cell lines as the preliminary subject of the research. As expected, we found that co-treatment caused a significant reduction of cell viability and more apoptosis. SAHA did not bring obvious cell cycle arrest. On the other hand, olaparib and co-treatment caused G2/M arrest. The data also showed that, with the soaring dose of SAHA, thereby shows an increment level of acetylation of histone H3 andα-tubulin in both singular and combined treatment. Besides, thymidylate synthase was further inhibited in combination compared to SAHA treated alone. In summary, we demonstrated the combination of olaparib with SAHA displayed favorable anti-cancer effect in SCLC cell lines. Results from our study may have clinical implications for designing novel SCLC treatments.