Clone and initial identification of differentially expressed genes of human small cell lung cancer (SCLC) multi-drug resistance (MDR) cell line.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. e21110-e21110
Author(s):  
G. Wu ◽  
K. Li
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xinying Li ◽  
Cen Chen ◽  
Zimu Wang ◽  
Jiaxin Liu ◽  
Wei Sun ◽  
...  

Abstract Background Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations will inevitably develop drug resistance after being treated with the third-generation EGFR-tyrosine kinase inhibitor (TKI), osimertinib. Recently, the drug resistance information transmitted by exosomal miRNAs has attracted much attention. However, the mechanism of exosome-derived miRNAs in osimertinib resistance remains unexplored. Methods We extracted and sequenced exosomes from the supernatant of the osimertinib-resistant cell line, H1975-OR, and the sensitive cell line, H1975. The results were compared with plasma exosome sequencing before and after the appearance of drug resistance in three NSCLC clinical patients treated with oral osimertinib. Exosome-derived miRNAs that had significantly increased expression levels after osimertinib resistance were screened for expanded validation in other 64 NSCLC patients. Results Cluster analysis of the target genes revealed that exosomal miRNAs participate in osimertinib resistance mechanisms through the activation of bypass pathways (RAS-MAPK pathway abnormality and PI3K pathway activation). Exosome-derived miR-184 and miR-3913-5p expression levels increased significantly after the onset of osimertinib resistance. Exosomal miR-3913-5p was associated with TNM stage, platelet count, tumor marker carcinoembryonic antigen, and distant metastases. In patients with EGFR exon 21 L858R mutation, the increased expression levels of miR-184 and miR-3913-5p derived from serum exosomes indicated osimertinib resistance. Similarly, for T790M-positive patients, the level of exosome-derived miR-3913-5p can be used as a predictive marker for osimertinib resistance. Conclusions The expression levels of miR-184 and miR-3913-5p derived from exosomes in the peripheral blood of NSCLC patients could be used as biomarkers to indicate osimertinib resistance. Graphic Abstract


Author(s):  
Zi-Ning Lei ◽  
Qiu-Xu Teng ◽  
Wei Zhang ◽  
Ying-Fang Fan ◽  
Jing-Quan Wang ◽  
...  

While topotecan (TPT) is a first- and second-line chemotherapeutic drug in treating lung cancer, the development of drug resistance in tumors still reserves as a major obstacle to chemotherapeutic success. Therefore, a better understanding of the mechanisms of topotecan resistance is critical. In this study, the first topotecan-resistant human non-small cell lung cancer (NSCLC) cell line, termed NCI-H460/TPT10, was established from the parental NCI-H460 cell line. NCI-H460/TPT10 cells exhibited a 394.7-fold resistance to TPT, and cross-resistance to SN-38, mitoxantrone, and doxorubicin, compared to parental NCI-H460 cells. Overexpression of ABCG2 localized on the cell membrane, but not ABCB1 or ABCC1, was found in NCI-H460/TPT10 cells, indicating that ABCG2 was likely to be involved in topotecan-resistance. This was confirmed by the abolishment of drug resistance in NCI-H460/TPT10 cells after ABCG2 knockout. Moreover, the involvement of functional ABCG2 as a drug efflux pump conferring multidrug resistance (MDR) was indicated by low intracellular accumulation of TPT in NCI-H460/TPT10 cells, and the reversal effects by ABCG2 inhibitor Ko143. The NCI-H460/TPT10 cell line and its parental cell line can be useful for drug screening and developing targeted strategies to overcome ABCG2-mediated MDR in NSCLC.


2017 ◽  
Vol 7 (3) ◽  
Author(s):  
Chukwumaobim D.U. Nwokwu ◽  
Sameera R. Samarakoon ◽  
Desiree N. Karunaratne ◽  
Nuwanthi P. Katuvawila ◽  
Meran K. Ediriweera ◽  
...  

2021 ◽  
Vol 27 ◽  
pp. 101089
Author(s):  
Kazuo Ohara ◽  
Shintaro Kinoshita ◽  
Jun Ando ◽  
Yoko Azusawa ◽  
Midori Ishii ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document