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Suberoylanilide hydroxamic acid overcomes erlotinib-acquired resistance via phosphatase and tensin homolog deleted on chromosome 10-mediated apoptosis in non-small cell lung cancer
- Source :
- Chinese Medical Journal, Vol 133, Iss 11, Pp 1304-1311 (2020), Chinese Medical Journal
- Publication Year :
- 2020
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2020.
-
Abstract
- Background:. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as erlotinib and gefitinib, are widely used to treat non-small cell lung cancer (NSCLC). However, acquired resistance is unavoidable, impairing the anti-tumor effects of EGFR-TKIs. It is reported that histone deacetylase (HDAC) inhibitors could enhance the anti-tumor effects of other antineoplastic agents and radiotherapy. However, whether the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) can overcome erlotinib-acquired resistance is not fully clear. Methods:. An erlotinib-resistant PC-9/ER cell line was established through cell maintenance in a series of erlotinib-containing cultures. NSCLC cells were co-cultured with SAHA, erlotinib, or their combination, and then the viability of cells was measured by the 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and apoptosis was determined by flow cytometry and western blotting. Finally, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was assessed by western blotting. Results:. The half-maximal inhibitory concentration of parental PC-9 cells was significantly lower than the established erlotinib-acquired resistant PC-9/ER cell line. PC-9/ER cells demonstrated reduced expression of PTEN compared with PC-9 and H1975 cells, and the combination of SAHA and erlotinib significantly inhibited cell growth and increased apoptosis in both PC-9/ER and H1975 cells. Furthermore, treating PC-9/ER cells with SAHA or SAHA combined with erlotinib significantly upregulated the expression of PTEN mRNA and protein compared with erlotinib treatment alone. Conclusions:. PTEN deletion is closely related to acquired resistance to EGFR-TKIs, and treatment with the combination of SAHA and erlotinib showed a greater inhibitory effect on NSCLC cells than single-drug therapy. SAHA enhances the suppressive effects of erlotinib in lung cancer cells, increasing cellular apoptosis and PTEN expression. SAHA can be a potential adjuvant to erlotinib treatment, and thus, can improve the efficacy of NSCLC therapy.
- Subjects :
- Lung Neoplasms
lcsh:Medicine
Apoptosis
Erlotinib Hydrochloride
03 medical and health sciences
0302 clinical medicine
Gefitinib
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Tensins
medicine
Humans
Tensin
PTEN
Histone deacetylase
Epidermal growth factor receptor
Lung cancer
Protein Kinase Inhibitors
neoplasms
Cell Proliferation
Vorinostat
biology
Chromosomes, Human, Pair 10
Cell growth
Chemistry
lcsh:R
SAHA
Original Articles
General Medicine
medicine.disease
Xenograft Model Antitumor Assays
respiratory tract diseases
ErbB Receptors
Erlotinib
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Cancer research
biology.protein
Acquired resistance
Tyrosine kinase
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 25425641 and 03666999
- Volume :
- 133
- Database :
- OpenAIRE
- Journal :
- Chinese Medical Journal
- Accession number :
- edsair.doi.dedup.....24dd4e87601ccdd169251827e5696863