J Cancer 2020; 11(24):7216-7223. doi:10.7150/jca.46461

Research Paper

In Vitro and in Vivo Efficacy of NBDHEX on Gefitinib-resistant Human Non-small Cell Lung Cancer

Huanhuan Sha1,2,*, Shuchen Dong1,*, Chen Yu1,*, Renrui Zou1,2, Yue Zhu1,2, Ya Lu1,2, Junying Zhang1, Haixia Cao1, Dan Chen1,✉, Jianzhong Wu1,✉, Jifeng Feng1,✉

1. The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Baiziting42, Nanjing 210009, China
2. The Forth Clinical School of Nanjing Medical University, Nanjing, 210009, China
* These authors contributed equally to this work.

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Citation:
Sha H, Dong S, Yu C, Zou R, Zhu Y, Lu Y, Zhang J, Cao H, Chen D, Wu J, Feng J. In Vitro and in Vivo Efficacy of NBDHEX on Gefitinib-resistant Human Non-small Cell Lung Cancer. J Cancer 2020; 11(24):7216-7223. doi:10.7150/jca.46461. Available from https://www.jcancer.org/v11p7216.htm

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Abstract

Gefitinib, a first-generation EGFR tyrosine kinase inhibitor (EGFR-TKI), is recommended for treatment of non-small cell lung cancer (NSCLC) patients who harbor activating EGFR mutations. However, the tumors of most patients initially sensitive to gefitinib will develop resistance within several months of therapy. Drug resistance is a major obstacle to NSCLC treatment. The novel glutathione transferase P1 (GSTPi) inhibitor 6-(7-nitro-2, 1, 3-benzoxadiazol-4-ylthio) hexanol (NBDHEX) has recently been shown to be active against tumors. In this study, we investigated the in vitro and in vivo efficacy of NBDHEX against NSCLC. Treatment with NBDHEX inhibited GSTpi enzymatic activity and promoted apoptosis of gefinitb-resistant NSCLC cells. Moreover, NBDHEX reduced tumor growth in mice. These findings indicated that NBDHEX is a good candidate for treatment of NSCLC patients, and that NBDHEX offers a new approach to cancer therapy.

Keywords: NBDHEX, gefitinib-resistant, NSCLC