ArticleScientific reports2015
Development of trastuzumab-resistant human gastric carcinoma cell lines and mechanisms of drug resistance.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 60 citations in OpenAlex.
- NEK2 promotes trastuzumab resistance in gastric cancer through WTAP/YTHDF1-dependent m6A regulation of FN1.Molecular biology reports · 2026Article
- The impact of the PI3K/AKT/mTOR signaling pathway on trastuzumab resistance in HER2-positive gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Acquired resistance of cancer therapies: Mechanisms and perspectives.Chinese medical journal · 2026Review
- Targeting LINC00665/miR-199b-5p/SERPINE1 axis to inhibit trastuzumab resistance and tumorigenesis of gastric cancer via PI3K/AKt pathway.Non-coding RNA research · 2025Article
- Novel immunotherapeutic approaches in gastric cancer.Precision clinical medicine · 2024Review
- Review
- Proteomics and Bioinformatics Identify Drug-Resistant-Related Genes with Prognostic Potential in Cholangiocarcinoma.Biomolecules · 2024Article
- YAP inhibition overcomes adaptive resistance in HER2-positive gastric cancer treated with trastuzumab via the AKT/mTOR and ERK/mTOR axis.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
- Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Clinical application of targeted tumour sequencing tests for detecting ERBB2 amplification and optimizing anti-HER2 therapy in gastric cancer.BMC cancer · 2024Article
- HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments.Cancers · 2024Review
- Novel HER2-targeted therapy to overcome trastuzumab resistance in HER2-amplified gastric cancer.Scientific reports · 2023Article
- Anticancer Peptides Derived from Aldolase A and Induced Tumor-Suppressing Cells Inhibit Pancreatic Ductal Adenocarcinoma Cells.Pharmaceutics · 2023Article
- Lipid Metabolism Reprogramming and Trastuzumab Resistance in Breast Cancer Cell Lines Overexpressing the ERBB2 Membrane Receptor.Membranes · 2023Article
- Statins enhance the efficacy of HER2-targeting radioligand therapy in drug-resistant gastric cancers.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Insulin and the insulin receptor collaborate to promote human gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Article
- RGS1 serves as an antitumor target to inhibit proliferation of NICN87-DR cells and tumor growth in the gastric cancer mouse model.Turkish journal of biology = Turk biyoloji dergisi · 2022Article
- miR-301a-3p induced by endoplasmic reticulum stress mediates the occurrence and transmission of trastuzumab resistance in HER2-positive gastric cancer.Cell death & disease · 2021Article
- Enhanced Antitumor Effect of Trastuzumab and Duligotuzumab or Ipatasertib Combination in HER-2 Positive Gastric Cancer Cells.Cancers · 2021Article
- ARPP-19 Mediates Herceptin Resistance via Regulation of CD44 in Gastric Cancer.OncoTargets and therapy · 2020Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trastuzumab has been successfully employed for the treatment of Her-2-positive gastric cancer. However, there are problems with both primary and secondary resistance to trastuzumab. In this study, we employed the human gastric carcinoma cell line NCI-N87 with high Her-2 expression to create trastuzumab-resistant NCI-N87/TR cells by stepwise exposure to increasing doses of trastuzumab. Western blotting and Real-time PCR were conducted to detect protein and gene levels. Compared with NCI-N87 cells, the expression of P-IGF-1R and P-AKT proteins was significantly increased in NCI-N87/TR cells (both P = 0.000), while PTEN gene and protein expression showed a significant decrease (both P = 0.000). In addition, mutations of the PTEN gene were detected at exons 5, 7, and 8. The sensitivity of NCI-N87/TR cells to trastuzumab was increased by transfection with the PTEN gene, or by incubation with a PI3K inhibitor (LY294002) or an IGF-IR inhibitor (AG1024), as well as siRNA targeting PI3K p110 or IGF-1R. Taken together, our findings showed that activation of the PI3K-AKT signaling pathway was one of the major mechanisms leading to resistance of NCI-N87/TR gastric cancer cells to trastuzumab, which was probably associated with PTEN gene down-regulation and mutation, as well as with over-activity of the IGF-1R signaling pathway.
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