MALAT1 reduces the sensitivity of EGFR-wild-type non-small cell lung cancer to gefitinib

Xiaoyu Wang; Shijun LI

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MALAT1 reduces the sensitivity of EGFR-wild-type non-small cell lung cancer to gefitinib

VernacularTitle:MALAT1降低非小细胞肺癌对吉非替尼药物敏感性的研究
Author: Xiaoyu WANG ; Shijun LI
Keywords: Carcinoma,non-small-cell lung; RNA,long noncoding; Microbial sensitivity tests
From: Chinese Journal of Laboratory Medicine 2017;40(1):55-59
CountryChina
Language:Chinese
Abstract: Objective To investigate serum metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in non-small cell lung cancer (NSCLC) and observe gefitinib drug sensitivity before and after transfecting MALAT1-siRNA in epidermal growth factor receptor ( EGFR ) wild-type cell line A549.Discussing the relationship between MALAT 1 and epidermal growth factor receptor-tyrosine kinase inhibitor ( EGFR-TKI) drug resistance.Methods Serum MALAT1 was quantified by qRT-PCR in 90 cases of NSCLC, 30 cases of lung benign tumor and 30 cases of healthy people in the First Affiliated Hospital of Dalian Medical University during April to September in 2015.MALAT1 expression in cancer cells were detected in the cell lines A549, H1299, 95D and HCC827.The half maximal inhibitory concentration ( IC50) of gefitinib in cells before and after transfecting MALAT 1-siRNA were analyzed by cell proliferation toxicity test ( CCK).Flow cytometry technology was used to evaluate the apoptosis rates.One-way analysis of variance was statisticed between groups.Results Serum MALAT1 expression was increased in NSCLC compared with healthy control group ( NSCLC =1.88 ±2.51, Healthy control group =1, t=3.347, P<0.01).MALAT1 was over expressed in the EGFR wild-type cell lines compared with the EGFR mutant cell lines(HCC827=1, A549=4.44 ±1.05, 95D=3.55 ±0.63,H1299 =1.44 ±0.05).The IC50 value of gefitinib was declined 32.1% by silencing MALAT1.The results of flow cytometry showed an increasing apoptosis rate after silencing MALAT1 in A549 cells[NC=(9.20 ±1.85 )%, M=(10.24 ±3.43)%, NC+G=( 14.57 ±0.41 )%, M +G =( 21.48 ±2.47 )%].Conclusions Serum MALAT1 reflected the progression of NSCLC.Silencing MALAT1 resulted in enhancement in sensitivity to gefitinib in A549 cell line.It prompted the partly reversal of gefitinib resistance by MALAT1.