J Cancer 2020; 11(3):559-569. doi:10.7150/jca.35792

Research Paper

Nedaplatin reduces multidrug resistance of non-small cell lung cancer by downregulating the expression of long non-coding RNA MVIH

Changwen Jing1*, Zhuo Wang1*, Rui Lou2*, Jianzhong Wu1, Chen Shi2, Dan Chen1, Rong Ma1, Siwen Liu1, Haixia Cao1✉, Jifeng Feng2✉

1. Research Center for Clinical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
2. Department of Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
*These authors have contributed equally to this work

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Citation:
Jing C, Wang Z, Lou R, Wu J, Shi C, Chen D, Ma R, Liu S, Cao H, Feng J. Nedaplatin reduces multidrug resistance of non-small cell lung cancer by downregulating the expression of long non-coding RNA MVIH. J Cancer 2020; 11(3):559-569. doi:10.7150/jca.35792. Available from http://www.jcancer.org/v11p0559.htm

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Abstract

Cisplatin based chemotherapy is the standard treatment for non-small cell lung cancer (NSCLC). However, drug resistance emergences after treatment. Long non-coding RNA microvascular invasion in hepatic cancer (MVIH) plays an important role in drug resistance in a variety of cancers. This study investigates the role of nedaplatin on multidrug resistance in NSCLC and its relationship with MVIH. Lung cancer A549 and H1650 cells were treated with cisplatin to obtain multidrug resistant A549/DDP and H1650/ DDP cells. A549/DDP and H1650/ DDP cells were treated with nedaplatin, MVIH siRNA and siRNA NC. It was found that both MVIH siRNA and nedaplatin significantly reduce the mRNA expression of MVIH in A549/DDP and H1650/ DDP cells. MTT assay showed that the proliferation of MDR cells was significantly higher than that of other cells. Nedaplatin and MVIH siRNA significantly inhibit the proliferation of A549 and H1650 cells. The results of colony formation assay were consistence with MTT results. Nedaplatin and MVIH siRNA significantly reduced colony formation in MDR cells. Flow cytometry showed that NDP and MVIH siRNA significantly decrease the proportion of cells in G0/G1 and increase the proportion of cells in S phase compared with untreated and MDR cells. The apoptotic rate of MDR cells was significantly lower than that of other cells, while the apoptosis rate of cells in NDP and MVIH siRNA group was significantly higher than that of the other three groups of cells. Wound healing assay and Transwell chamber experiments confirmed that both NDP and MVIH siRNA significantly reduced the migration and invasion abilities of MDR cells. The expression of E-cadherin in MDR cells was significantly lower than that in untreated cells, and the expression of N-cad, α-SMA and Vimentin significantly increased in the MDR cells. NPD and MVIH siRNA reverse the EMT process. In conclusion, LncRNA MVIH are upregulated in drug resistant NSCLC cells. Nedaplatin can reduce the expression of MVIH and reverse EMT process, thus reversing the drug resistance of cisplatin in non-small cell lung cancer cells.

Keywords: nedaplatin, lncRNA, MVIH, NSCLC, multidrug resistance, EMT