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Increased ABCC2 expression predicts cisplatin resistance in non‐small cell lung cancer
Author(s) -
Chen Yun,
Zhou Hongying,
Yang Sifu,
Su Dan
Publication year - 2021
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3577
Subject(s) - multidrug resistance associated protein 2 , cisplatin , gene knockdown , a549 cell , pharmacology , cancer research , multiple drug resistance , downregulation and upregulation , lung cancer , cytotoxicity , drug resistance , biology , medicine , atp binding cassette transporter , chemistry , apoptosis , oncology , transporter , in vitro , chemotherapy , biochemistry , genetics , gene
Long‐term use of platinum‐based drugs can cause non‐small cell lung cancer (NSCLC) to develop extremely strong drug resistance. Increasing the drug dosage does not have better treatment effects and could lead to serious complications. High levels of drug resistance are considered to be characteristic of human tumours and are usually mediated by genes related to multidrug resistance. Multidrug resistance‐associated protein 2 (ABCC2), an ATP‐binding cassette multidrug resistance transporter, was found to be overexpressed in various human cancers. In this study, we found that ABCC2 was also upregulated in cisplatin (DDP)‐resistant A549 cells (A549/DDP). Functional studies demonstrated that ABCC2 knockdown reversed DDP resistance and promoted G1 phase arrest in A549/DDP cells, and PARP and caspase‐3 were activated in A549/DDP cells following ABCC2 knockdown. In vivo, ABCC2 knockdown enhanced the cytotoxicity of DDP to subcutaneous A549 tumours. Together, these results suggest that ABCC2 may be a potential therapeutic strategy for overcoming DDP resistance in NSCLC patients. Significance of the study In this study, we investigated the role of ABCC2 in cisplatin resistance of NSCLC cells. Our data show that ABCC2 expression was associated with resistance to cisplatin and that knockdown ABCC2 could reverse cisplatin resistance in NSCLC cells. Taken together, our study suggests that reducing the expression of ABCC2 could become an important strategy for enhancing the sensitivity of NSCLC cells to cisplatin.