465P - 5-aza-2'-deoxycytidine enhances chemo sensitivity to cisplatin by up-regulating miRNA-320a in lung adenocarcinoma cells harboring wild-type EGFR

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Anticancer agents
Cancer Biology
Non-Small-Cell Lung Cancer, Metastatic
Presenter Fang Wu
Citation Annals of Oncology (2016) 27 (suppl_9): ix139-ix156. 10.1093/annonc/mdw594
Authors F. Wu, C. Hu
  • Oncology, Central South University Xiangya No.2 Hospital, 410011 - Changsha/CN

Abstract

Background

Cisplatin resistance is a major obstacle in the treatment of non-small cell lung cancer, especially in lung adenocarcinoma cells harboring wild-type EGFR. Its mechanism has not been fully elucidated. MicroRNAs (miRNA) may play a role in the modulation of chemo sensitivity-related pathways in cancer cells. And the expression of miRNAs were involved by demethylating agent 5-aza-2'-deoxycytidine (5-Aza-dc). This study was designed to determine that whether 5-Aza-dc may increase the sensitivity of lung adenocarcinoma wild-type EGFR cells A549/DDP to cisplatin by regulating the expression of miRNAs.

Methods

The EGFR gene mutation of A549/DDP cells were examined by Qpcr-HRM. MTT method for test of cisplatin-resistance reverse index of A549/DDP cells treated by 5-Aza-dc. MiRNA microarray was employed to compare miRNA expression differences between A549/DDP cells and the same cells treated by 5-Aza-dc; the results of microarray were confirmed by RT-qPCR. TargeScan, PicTar2005 and Miranda v5.1 were used to predict the target genes of miRNA.

Results

A549/DDP was wild-type EGFR cell line. Non-toxic dose of 5-Aza-dc could reduce the IC50 of cisplatin from 39.39±2.86μM to 17.21±3.13μM, cisplatin-resistance reverse index was 2.29. The miRNA microarray presented that 27 miRNAs were significantly up-regulated in A549/DDP cells treated by 5-Aza-dc. Among the top 3, miR-320a exhibited 3-fold changes. Bioimformatic analysis showed that E2F1 and FOXO3 was the targeted genes of miR-320a.

Conclusions

The study demonstrate that 5-Aza-dc can increase sensitivity to cisplatin in lung adenocarcinoma cells harboring wild-type EGFR. And the up-regulation of miR-320a expression may provide a new potential mechanisms of the enhancement.

Clinical trial indentification

Legal entity responsible for the study

N/A

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.