ArticleToxicology and applied pharmacology2017
Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells.
Article in Toxicology and applied pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 18 citations in OpenAlex.
- Whole genome characterization of patient-derived lung cancer organoids.Translational lung cancer research · 2025Article
- Single-cell and Bulk RNA-Seq reveal angiogenic heterogeneity and microenvironmental features to evaluate prognosis and therapeutic response in lung adenocarcinoma.Frontiers in immunology · 2024Article
- CRM1 expression: association with high prognostic value in laryngeal cancer.Turkish journal of medical sciences · 2023Article
- Proteome derangement in malignant epithelial cells and its stroma following exposure to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.Archives of toxicology · 2023Article
- Prognosis and personalized treatment prediction in lung adenocarcinoma: AnFrontiers in pharmacology · 2023Article
- A novel circ_MACF1/miR-942-5p/TGFBR2 axis regulates the functional behaviors and drug sensitivity in gefitinib-resistant non-small cell lung cancer cells.BMC pulmonary medicine · 2022Article
- Lipidomics reveals that sustained SREBP-1-dependent lipogenesis is a key mediator of gefitinib-acquired resistance in EGFR-mutant lung cancer.Cell death discovery · 2021Article
- Relationship between long non-coding RNA PCAT-1 expression and gefitinib resistance in non-small-cell lung cancer cells.Respiratory research · 2021Article
- BST2 promotes growth and induces gefitinib resistance in oral squamous cell carcinoma via regulating the EGFR pathway.Archives of medical science : AMS · 2021Article
- Qing-Kai-Ling Injection Acts Better Than Shen-Fu Injection in Enhancing the Antitumor Effect of Gefitinib in Resistant Non-Small Cell Lung Cancer Models.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Synergistic effects of Bcl-2 inhibitors with AZD9291 on overcoming the acquired resistance of AZD9291 in H1975 cells.Archives of toxicology · 2020Article
- Drug resistance occurred in a newly characterized preclinical model of lung cancer brain metastasis.BMC cancer · 2020Article
- Overcoming acquired resistance of gefitinib in lung cancer cells without T790M by AZD9291 or Twist1 knockdown in vitro and in vivo.Archives of toxicology · 2019Article
- Development and characterisation of a panel of phosphatidylinositide 3-kinase - mammalian target of rapamycin inhibitor resistant lung cancer cell lines.Scientific reports · 2018Article
- Tumor-associated macrophage-derived cytokines enhance cancer stem-like characteristics through epithelial-mesenchymal transition.OncoTargets and therapy · 2018Review
- The lncRNA RHPN1-AS1 downregulation promotes gefitinib resistance by targeting miR-299-3p/TNFSF12 pathway in NSCLC.Cell cycle (Georgetown, Tex.) · 2018Article
- Targeting of nucleo‑cytoplasmic transport factor exportin 1 in malignancy (Review).Medicine internationalReview
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2 authors at 1 institution in 1 country.
Funding
Abstract
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib has demonstrated dramatic clinical efficacy in non-small cell lung cancer (NSCLC) patients. However, its therapeutic efficacy is ultimately limited by the development of acquired drug resistance. The aim of this study was to explore the potential utility of chromosome region maintenance 1 (CRM1) inhibitor leptomycin B (LMB) in combination with gefitinib to overcome primary and acquired gefitinib resistance in NSCLC cells. The combinative effects of gefitinib and LMB were evaluated by MTT and its underlining mechanism was assessed by flow cytometry and Western blot. LMB displayed a synergistic effect on gefitinib-induced cytotoxicity in A549 (IC50: 25.0±2.1μM of gefitinib+LMB vs. 32.0±2.5μM of gefitinib alone, p<0.05). Gefitinib+LMB caused a significantly different cell cycle distribution and signaling pathways involved in EGFR/survivin/p21 compared with gefitinib. A549 cells then were treated with progressively increased concentrations of gefitinib (A549GR) or in combination with LMB (A549GLR) over 10months to generate gefitinib resistance. IC50 of gefitinib in A549GLR (37.0±2.8μM) was significantly lower than that in A549GR (53.0±3.0μM, p<0.05), which indicates that LMB could reverse gefitinib-induced resistance in A549. Further mechanism investigation revealed that the expression patterns of EGFR pathway and epithelial-mesenchymal transition (EMT) markers in A549, A549GR, and A549GLR were significantly different. In conclusion, LMB at a very low concentration (0.5nM) combined with gefitinib showed synergistic therapeutic effects and ameliorated the development of gefitinib-induced resistance in lung cancer cells.
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