Work

Differential Expression And Effects Of Peroxiredoxin-6 On Drug Resistance And Cancer Stem Cell-Like Properties In Non-Small Cell Lung Cancer

Year: 2019

Type: article

Abstract: OBJECTIVE: Cancer stem-like cells (CSC) are thought to be involved in the cisplatin resistance of tumors. This study was designed to investigate the effect of PRDX6 on CSCs present in cisplatin-resistant non-small cell lung cancer (NSCLC) tumors. MATERIALS AND METHODS: values for cisplatin in treatment of CSCs were detected using the CCK8 assay. Then the isolated cells were identified using CD133. Wnt/β-catenin expression was evaluated by Western blot assays. Specimens of tumor and adjacent para-carcinoma tissue were collected from 30 NSCLC patients and examined by immunohistochemistry (IHC), qRT-PCR, and Western blotting to determine and compare their levels of PRDX6 and CD133 expression. Finally, siRNA-mediated silencing of PRDX6 was employed with both types of CSCs to determine the impact of PRDX6 on CD133 enrichment by flow cytometry, cell viability, and sphere formation ability. RESULTS: High levels of PRDX6 and CD133 expression were detected in samples of tumor tissue from NSCLC patients, and expression of PRDX6 and CD13 presented a positive relationship. Increasing levels of cisplatin resistance and upregulated levels of PRDX6, ABCG2, Wnt, and β-catenin expression were detected in CD133+/ABCG2+ H1299 and A549 CSCs. Transfection with siRNA targeting PRDX6 changed these cellular characteristics by decreasing the levels of PRDX6, ABCG2, Wnt, and β-catenin expression. We further demonstrated that exogenous silencing of PRDX6 effectively inhibited the sphere formation ability of CSCs and re-sensitized them to cisplatin. CONCLUSION: Our results strongly suggest that PRDX6 promotes cisplatin resistance in human lung cancer cells by promoting the stem-like properties of cancer cells. Our findings also suggest PRDX6 as a target for treating cisplatin resistant NSCLC.

Source: OncoTargets and Therapy

DOI: 10.2147/ott.s211125

Authors: Jun Xu, Qiang Su, Mingxia Gao, Qingsong Liang, Junfeng Li, Xu Chen

Institutions: North Sichuan Medical University, Nanchong Central Hospital

Language: English

Topic: Cancer Cells and Metastasis

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,836