title: Hypermethylation of ATP-binding cassette B1 (ABCB1) multidrug resistance 1 (MDR1) is associated with cisplatin resistance in the A549 lung adenocarcinoma cell line.
abstract: Development of multiple drug resistance has been attributed to the overexpression of the ATP-binding cassette B1 (ABCB1) gene. In this study, the major purpose was to assess the expression and methylation levels of ABCB1 in human lung adenocarcinoma and to reveal the relationship between these processes and acquisition of cisplatin (DDP) resistance in the human cancer cell line A549. Methylation and expression levels of the ABCB1 gene ABCB1 in clinical human lung tissue were assessed using bisulphite sequencing, reverse transcription real-time PCR (RT2-PCR) and Western blot methods. Cell viability, DDP resistance and apoptosis of A549 cells were evaluated using the Cell Counting Kit-8 and fluorescence-activated cell sorter analysis. Our results showed that the onset of resistance to the cisplatin analogue, DDP, was associated with hypermethylation of the ABCB1 gene. Expression of the ABCB1 gene was enhanced at both mRNA and protein levels. Treatment with 5-Aza-C contributed to the hypomethylation of the ABCB1 gene and decreased ABCB1 protein expression in A549 cells. In conclusion, this in vitro and human tissue study of lung adenocarcinoma cells demonstrated that hypermethylation of the ABCB1 gene correlated with increased gene expression and was associated with the acquisition of resistance to the cisplatin analogue, DDP in human lung adenocarcinoma cells. Taken together, our study highlighted the connection between increased ABCB1 methylation level and upregulated expression of the gene in lung cancer. Moreover, the abnormally high expression of ABCB1 in A549 cells contributed to the development of the DDP resistance.
authors.affiliation: Department of Cardiothoracic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
authors.forename: Angui
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Cardiothoracic Surgery, The 2nd Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Thoracic Surgery, Xiangya Hospital Cental South University, Changsha, Hunan, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Lai
authors.affiliation: Department of Cardiothoracic Surgery, The 2nd Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
authors.forename: Bangqing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Cardiothoracic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
authors.forename: Haiyong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiothoracic Surgery, The 2nd Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
authors.forename: Yinhui
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Cardiothoracic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Cardiothoracic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Cardiothoracic Surgery, Nanxishan Hospital of Guangxi Province, Guilin, Guangxi, China.
authors.forename: Zhenzong
authors.initials: Z
authors.lastname: Du
mesh_terms: D000072283:A549 Cells; D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019175:DNA Methylation; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D001374:Azacitidine; D002945:Cisplatin
keywords: ATP-binding cassette B1; Biomarker; Hypermethylation; diamminedichloroplatinum; lung cancer