ArticleJournal of cancer research and clinical oncology2019
Co-targeting PI3K/Akt and MAPK/ERK pathways leads to an enhanced antitumor effect on human hypopharyngeal squamous cell carcinoma.
Article in Journal of cancer research and clinical oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Current Advances of Treatments, Therapeutic Targets, Biomarkers, Novel Drugs, and Machine Learning for Hypopharyngeal Squamous Cell Carcinoma.World journal of otorhinolaryngology - head and neck surgery · 2026Review
- 3,3'-((3-Hydroxyphenyl)azanediyl)dipropionic Acid Derivatives as a Promising Scaffold Against Drug-Resistant Pathogens and Chemotherapy-Resistant Cancer.Pathogens (Basel, Switzerland) · 2025Article
- Redefining bladder cancer treatment: innovations in overcoming drug resistance and immune evasion.Frontiers in immunology · 2025Review
- Experimental Investigation of the Effects of Photobiomodulation Therapy on the Viability, Migration, and Gene Expression of Human Gingival Fibroblasts.Journal of lasers in medical sciences · 2025Article
- RIT1 Promotes the Proliferation of Gliomas Through the Regulation of the PI3K/AKT/c-Myc Signalling Pathway.Journal of cellular and molecular medicine · 2025Article
- Disulfidptosis-related gene signatures as prognostic biomarkers and predictors of immunotherapy response in HNSCC.Frontiers in immunology · 2024Article
- Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK).Journal of enzyme inhibition and medicinal chemistry · 2023Review
- Role of PPARG in Chemosensitivity-Regulating Network for Hypopharyngeal Squamous Cell Carcinoma.PPAR research · 2023Article
- Antitumor effects of valdecoxib on hypopharyngeal squamous carcinoma cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2022Article
- Role of PI3K/AKT pathway in squamous cell carcinoma with an especial focus on head and neck cancers.Cancer cell international · 2022Review
- Cancer-cell-biomimetic nanoparticles systemically eliminate hypoxia tumors by synergistic chemotherapy and checkpoint blockade immunotherapy.Acta pharmaceutica Sinica. B · 2022Article
- Precision drugging of the MAPK pathway in head and neck cancer.NPJ genomic medicine · 2022Review
- Article
- Structural effects of morpholine replacement in ZSTK474 on Class I PI3K isoform inhibition: Development of novel MEK/PI3K bifunctional inhibitors.European journal of medicinal chemistry · 2022Article
- AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-κB signaling pathway.Cell & bioscience · 2021Article
- ASN007 is a selective ERK1/2 inhibitor with preferential activity against RAS-and RAF-mutant tumors.Cell reports. Medicine · 2021Article
- BKM120 sensitizes glioblastoma to the PARP inhibitor rucaparib by suppressing homologous recombination repair.Cell death & disease · 2021Article
- Effects of Maackia amurensis seed lectin (MASL) on oral squamous cell carcinoma (OSCC) gene expression and transcriptional signaling pathways.Journal of cancer research and clinical oncology · 2021Article
- Copy Number Alterations in Hepatoblastoma: Literature Review and a Brazilian Cohort Analysis Highlight New Biological Pathways.Frontiers in oncology · 2021Article
- Antitumour Effects of Astaxanthin and Adonixanthin on Glioblastoma.Marine drugs · 2020Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
purposeThe present study aims to determine whether co-targeting PI3K/Akt and MAPK/ERK pathways in human hypopharyngeal squamous cell carcinoma (HSCC) is a potential anticancer strategy.
methodsWe retrospectively analyzed the clinical data of HSCC patients, and the phosphorylation status of Akt and Erk in HSCC and tumor adjacent tissues was evaluated by immunohistochemistry. MTT and colony formation assay were performed to determine the anti-proliferative effect of PI3K/mTOR inhibitor GDC-0980 and MEK inhibitor Refametinib on HSCC cell line Fadu. Wound-healing and Transwell migration assay were used to analyze the anti-migrative capability of the two drugs. The involved anti-tumor mechanism was explored by flow cytometry, qRT-PCR and western blot. The combinational anticancer effect of GDC-0980 and Refametinib was evaluated according to Chou and Talalay's method.
resultsThe levels of p-Akt and p-Erk were increased significantly with the progression of clinical stage of HSCC, suggesting PI3K/Akt and MAPK/ERK pathways might be associated with HSCC occurrence and progression. Furthermore, both GDC-0980 and Refametinib showed obvious antitumor effects on FaDu cells. Treatment by the two drugs arrested FaDu cell cycle progression in G1 phase, with reduction of cyclin D1 and p-Rb, in contrast to enhancement of p27. GDC-0980 inhibited FaDu cell migration and reduced metastasis related proteins including p-PKCζ, p-Integrin β1 and uPA. Combination use of GDC-0980 and Refametinib exhibited strong synergistic anti-tumor effect.
conclusionDual inhibition of PI3K/Akt and MAPK/ERK pathway by GDC-0980 and Refametinib might be a promising treatment strategy for HSCC patients.
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