Abstract 1159: Association of ALDH7A1 overexpression with chemotherapy resistance and cancer stem cell in lung cancer

Abstract

Abstract Aldehyde dehydrogenases (ALDHs) play a major role in the oxidation of aldehydes. Certain isoforms of ALDH is related to cancer stem cells (CSCs) responsible for tumor initiating, drug resistance and metastasis. ALDH1A1 and ALDH3A1 have been known for CSC markers of lung cancer. Since these two isoforms and ALDH7A1 are involved in cellular structural and osmoregulatory function, we focused on function of ALDH7A1 in lung cancer. We established SN-38 resistant DMS53 (DMS53-SR) and SN-38 or gemcitabine resistant NCI-H23 (H23-SR or H23-GR, respectively) by intermittent and dose-escalating exposure of the agent. The expression of ALDH7A1 was upregulated in DMS53-SR and H23-SR/H23-GR compared with DMS53 and NCI-H23, respectively. ALDH7A1 expression was altered using a plasmid to overexpress ALDH7A1 in DMS53. ALDH7A1 overexpression led to a slight increase of IC50 of SN-38, upregulation of SOX2, and tumor sphere formation. Overexpression of ALDH7A1 in DMS53 have enhanced tumorigenic capacity in vivo. These data suggested that ALDH7A1 might be a marker of CSC and a therapeutic target of lung cancer. Citation Format: Yuto Yasuda, Yuichi Sakamori, Hiroaki Ozasa, Hitomi Ajimizu, Tetsuya Oguri, Ken Maeno, Takahiro Tsuji, Takashi Nomizo, Tomoko Yamamoto, Hironori Yoshida, Toyohiro Hirai, Young Hak Kim. Association of ALDH7A1 overexpression with chemotherapy resistance and cancer stem cell in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1159.