Increased ABCC2 expression predicts cisplatin resistance in non‐small cell lung cancer

Abstract

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.

The Relationship Between Systemic Immune Inflammatory Index and Prognosis of Patients With Non-Small Cell Lung Cancer: A Meta-Analysis and Systematic Review

“…The treatment of NSCLC includes surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy ( 4 ). Nonetheless, the efficacy of these therapies in NSCLC patients remains dissatisfactory due to the lack of resultful indicators that can be utilized to predict the disease course and the widespread chemoresistance of NSCLC ( 5 ). Hence, it is necessary for researchers to identify exact biomarkers and potential therapeutic targets for NSCLC to improve survival.…”

Perftoran® Inhibits Hypoxia-Associated Resistance in Lung Cancer Cells to Carboplatin

“… Gatti et al (2009) stated that ATP-binding cassette transporters (ABC transporters) can control chemotherapy resistance. A recent study investigated the role of ABCC2 in the resistance of NSCLC cells to cisplatin, reporting that ABCC2 expression was associated with resistance to cisplatin and that ABCC2 knockdown could reverse cisplatin resistance in NSCLC cells and enhance the sensitivity of NSCLC cells to cisplatin ( Chen et al, 2021 ). Since tumors that were resistant to cisplatin exhibited cross-resistance to its platinum analog carboplatin, thereby limiting treatment options in such tumors ( Siddik, 2003 ), the findings of the ABCC2 knockdown support the results of the current study.…”

Targeting Drug Chemo-Resistance in Cancer Using Natural Products

“…Furthermore, overexpression of ABCC2 and ABCC3 has a pivotal effect on the resistance of multiple cytotoxic drugs such as methotrexate, cisplatin, doxorubicin, and etoposide [33,34]. These were found to potentiate the drug resistance in breast, liver, and lung cancers [34][35][36]. Accordingly, a deep understanding of ABC transporters (structure, physiology, overexpression, and mutations) has a promising role in innovating clinically effective anticancer drugs.…”