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. 2018 Jul:100:54-60.
doi: 10.1016/j.biocel.2018.05.003. Epub 2018 May 26.

NDRG1 disruption alleviates cisplatin/sodium glycididazole-induced DNA damage response and apoptosis in ERCC1-defective lung cancer cells

Lang He  1 , Kang Liu  2 , Xiaoshan Wang  3 , Hong Chen  4 , Jin Zhou  5 , Xun Wu  6 , Tao Liu  7 , Yongxue Yang  8 , Xuemei Yang  1 , Dandan Cui  1 , Guiqin Song  9 , Jun Wang  10 , Jianguo Lei  11
Affiliations

NDRG1 disruption alleviates cisplatin/sodium glycididazole-induced DNA damage response and apoptosis in ERCC1-defective lung cancer cells

Lang He et al. Int J Biochem Cell Biol. 2018 Jul.

Erratum in

Abstract

Background: Resistance to platinum-based chemotherapy becomes a major obstacle in lung cancer treatment. Compensatory activation of nucleotide excision repair (NER) pathway is the major mechanism accounting for cisplatin-resistance. We aimed at identifying additional regulators in NER-mediated chemoresistance in a hypoxic setting induced by sodium glycididazole (CMNa)-sensitized cisplatin chemotherapy of non-small cell lung cancer (NSCLC).

Methods: We performed an RNA-sequencing (RNA-Seq) analysis to identify the genes whose expression had been differentially regulated in NER-deficient cells that had been treated by cisplatin/CMNa. DNA damage, apoptosis, and correlational analysis between the differentially expressed gene and drug sensitivity were determined by Western blots, flow cytometry and Oncomine expression analysis.

Results: The stress response gene, NDRG1 (N-Myc downstream-regulated gene 1), was among the differentially expressed genes in NER-deficient cells upon treatment of cisplatin/CMNa. Downregulation of NDRG1 by ERCC1 (excision repair cross-complementing 1) could be a prevalent mechanism for drug resistance. Furthermore, lower NDRG1 level is observed in human lung cancer cells showing chemotherapeutic drug resistance compared with the drug-sensitive cells.

Conclusion: NDRG1 is an important modulator linking DNA damage response and hypoxia-related cellular stress response during the development of drug resistance to cisplatin/CMNa in lung cancer. Targeting both NDRG1 and ERCC1 may be a viable strategy for overcoming drug resistance in cancer therapy, and has significant clinical implications.

Keywords: CMNa; Chemotherapy; Cisplatin; Drug resistance; ERCC1; NDRG1; Nucleotide excision repair (NER) pathway; RNA-Seq.

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