ArticleJournal of experimental & clinical cancer research : CR2019
Sequence-dependent synergistic cytotoxicity of icotinib and pemetrexed in human lung cancer cell lines in vitro and in vivo.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
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- PD-L1 induces autophagy and primary resistance to EGFR-TKIs in EGFR-mutant lung adenocarcinoma via the MAPK signaling pathway.Cell death & disease · 2024Article
- Prognosis prediction of icotinib as targeted therapy for advanced EGFR-positive non-small cell lung cancer patients.Investigational new drugs · 2023Article
- Sequence-dependent synergistic effect of aumolertinib-pemetrexed combined therapy on EGFR-mutant non-small-cell lung carcinoma with pre-clinical and clinical evidence.Journal of experimental & clinical cancer research : CR · 2022Article
- Neurite Extension and Orientation of Spiral Ganglion Neurons Can Be Directed by Superparamagnetic Iron Oxide Nanoparticles in a Magnetic Field.International journal of nanomedicine · 2021Article
- Therapeutic efficacy and imaging assessment of the HER2-targeting chemotherapy drug ZInvestigational new drugs · 2020Article
- Synergistic combinations of paclitaxel and withaferin A against human non-small cell lung cancer cells.Oncotarget · 2020Article
- Chemotherapy Plus EGFR-TKI as First-Line Treatment Provides Better Survival for Advanced EGFR-Positive Lung Adenocarcinoma Patients: Updated Data and Exploratory In Vitro Study.Targeted oncology · 2020Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundRecent Clinical trials of administration of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in combination with standard first-line chemotherapy have failed to improve survival in patients with advanced NSCLC, However, the sequential treatment with EGFR-TKIs and chemotherapy is expected to improve survival of NSCLC. The aim of this study is to test the antiproliferative effect of pemetrexed combined with icotinib in different sequences on non-small cell lung cancer (NSCLC) cell lines to determine the optimal combination schedule, and subsequently elaborated the potential mechanisms.
methodsSix human lung cancer cell lines with wild-type or mutant EGFR gene were exposed to pemetrexed and icotinib combined in different sequences. Cell proliferation was examined by cell counting kit-8 (CCK-8) and colony formation assay; cell cycle and apoptosis were evaluated by flow cytometry; cell migration and invasion were measured by wound healing and transwell invasion assays respectively; protein expression was by detected by Western blot.
resultsThe growth inhibition effect of pemetrexed combined with icotinib on NSCLC cells were schedule-dependent in vitro and in vivo. Treatment with pemetrexed followed by icotinib (P-I) had significantly stronger anticancer ability than treatment with icotinib followed by pemetrexed (I-P) and concomitant treatment with pemetrexed and icotinib (P + I). Cell cycle analysis revealed that pemetrexed blocked cells in S phase, whereas icotinib arrested cells in G1 phase. We also found that icotinib markedly enhanced the pro-apoptotic activity of pemetrexed via cytochrome-C/Caspase/Bcl-2 signaling pathway. In addition, our results showed that pemetrexed alone increased the levels of p-EGFR, p-AKT and p-MAPK, which were inhibited by icotinib. Finally, we showed that the washout period of icotinib was no less than 96 h.
conclusionsSequential treatment of NSCLC cells with pemetrexed followed by icotinib had powerful antiproliferative effect, and it could become a novel effective combination therapy for NSCLC patients.
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