ArticleBMC cancer2017
Inhibition of PI3K/Akt/mTOR overcomes cisplatin resistance in the triple negative breast cancer cell line HCC38.
Article in BMC cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 103 citations in OpenAlex.
- Hedyotis diffusa and Scutellaria barbata enhance the anti-ovarian cancer effect of cisplatin through network pharmacology analysis and molecular docking technology.Scientific reports · 2026Article
- Spatial transcriptomics and single-cell analyses reveal the role of the cisplatin-resistant gene panel in NSCLC progression and the tumor microenvironment, identifying LOXL2 as a potential therapeutic target.Cancer cell international · 2026Article
- Medicarpin reduces cisplatin resistance and causes apoptosis by inhibiting the AKT/Bcl2 pathway in breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
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- Targeting Triple-Negative Breast Cancer: Resistance Mechanisms and Therapeutic Advancements.Cancer medicine · 2025Review
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- Future investigative directions for novel therapeutic targets in head and neck cancer.Expert review of anticancer therapy · 2024Review
- KIFC3 promotes the proliferation, migration and invasion of non-small cell lung cancer through the PI3K/AKT signaling pathway.Scientific reports · 2024Article
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- Trichostatin C Synergistically Interacts with DNMT Inhibitor to Induce Antineoplastic Effect via Inhibition of Axl in Bladder and Lung Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2024Article
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- Effect of Opioid Receptor Activation and Blockage on the Progression and Response to Treatment of Head and Neck Squamous Cell Carcinoma.Journal of clinical medicine · 2023Article
- Diclofenac Sensitizes Signet Ring Cell Gastric Carcinoma Cells to Cisplatin by Activating Autophagy and Inhibition of Survival Signal Pathways.International journal of molecular sciences · 2022Article
- A Systems Biology Approach to Investigate Kinase Signal Transduction Networks That Are Involved in Triple Negative Breast Cancer Resistance to Cisplatin.Journal of personalized medicine · 2022Article
- Eribulin Mesylate Improves Cisplatin-Induced Cytotoxicity of Triple-Negative Breast Cancer by Extracellular Signal-Regulated Kinase 1/2 Activation.Medicina (Kaunas, Lithuania) · 2022Article
- Carboxyl-Functionalized Carbon Nanotubes Loaded with Cisplatin Promote the Inhibition of PI3K/Akt Pathway and Suppress the Migration of Breast Cancer Cells.Pharmaceutics · 2022Article
- Knockdown of death receptor 5 antisense long noncoding RNA and cisplatin treatment modulate similar macromolecular and metabolic changes in HeLa cells.Turkish journal of biology = Turk biyoloji dergisi · 2022Article
- MicroRNAs as the critical regulators of Cisplatin resistance in ovarian cancer cells.Journal of ovarian research · 2021Review
- Pharmacologically Inhibiting Glycogen Synthase Kinase-3β Ameliorates Renal Inflammation and Nephrotoxicity in an Animal Model of Cisplatin-Induced Acute Kidney Injury.Biomedicines · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWidely established targeted therapies directed at triple negative breast cancer (TNBC) are missing. Classical chemotherapy remains the systemic treatment option. Cisplatin has been tested in TNBC but bears the disadvantage of resistance development. The purpose of this study was to identify resistance mechanisms in cisplatin-resistant TNBC cell lines and select targeted therapies based on these findings.
methodsThe TNBC cell lines HCC38 and MDA-MB231 were subjected to intermittent cisplatin treatment resulting in the 3.5-fold cisplatin-resistant subclone HCC38CisR and the 2.1-fold more resistant MDA-MB231CisR. Activation of pro-survival pathways was explored by immunostaining of phospho-receptor tyrosine kinases. Targeted therapies (NVP-AEW541, lapatinib and NVP-BEZ235) against activated pathways were investigated regarding cancer cell growth and cisplatin sensitivity.
resultsIn HCC38CisR and MDA-MB231CisR, phosphorylation of epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R) was observed. In HCC38CisR, treatment with NVP-AEW541 increased potency of lapatinib almost seven-fold, but both compounds could not restore cisplatin sensitivity. However, the dual phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor NVP-BEZ235 acted synergistically with cisplatin in HCC38CisR and fully restored cisplatin sensitivity. Similarly, NVP-BEZ235 increased cisplatin potency in MDA-MB231CisR. Furthermore, NVP-AEW541 in combination with lapatinib restored cisplatin sensitivity in MDA-MB231CisR.
conclusionSimultaneous inhibition of EGFR and IGF1R in cisplatin-resistant TNBC cell lines was synergistic regarding inhibition of proliferation and induction of apoptosis. Co-treatment with NVP-BEZ235 or with a combination of NVP-AEW541 and lapatinib restored cisplatin sensitivity and may constitute a targeted treatment option for cisplatin-resistant TNBC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.