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Updated: Jan 5, 2026
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Co-targeting PI3K/Akt and MAPK/ERK pathways leads to an enhanced antitumor effect on human hypopharyngeal squamous
Xiaolin Peng1,2, Yao Liu1,2, Shan Zhu1
1Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, 300070, Tianjin, China.
Purpose:
The 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.
Methods:
We 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.
Results:
The 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.
Conclusion:
Dual inhibition of PI3K/Akt and MAPK/ERK pathway by GDC-0980 and Refametinib might be a promising treatment strategy for HSCC patients.
Insights
Co-targeting PI3K/Akt and MAPK/ERK pathways with GDC-0980 and Refametinib shows promise for treating hypopharyngeal squamous cell carcinoma (HSCC). This combination therapy demonstrated synergistic anticancer effects in HSCC cells.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Hypopharyngeal squamous cell carcinoma (HSCC) is a challenging malignancy.
- The PI3K/Akt and MAPK/ERK signaling pathways are frequently implicated in cancer progression.
Purpose of the Study:
- To investigate the potential of co-targeting the PI3K/Akt and MAPK/ERK pathways as an anticancer strategy for HSCC.
- To evaluate the efficacy and mechanisms of dual inhibition using specific inhibitors.
Main Methods:
- Retrospective analysis of HSCC patient clinical data.
- Immunohistochemical evaluation of p-Akt and p-Erk levels.
- In vitro assessment of anti-proliferative and anti-migrative effects of GDC-0980 and Refametinib on FaDu cells.
- Mechanistic studies using flow cytometry, qRT-PCR, and Western blot.
- Synergistic effect evaluation using Chou and Talalay's method.
Main Results:
- Elevated p-Akt and p-Erk levels correlated with HSCC clinical stage progression.
- Both GDC-0980 and Refametinib exhibited significant antitumor effects on FaDu cells.
- Combination therapy demonstrated strong synergistic anticancer activity, including cell cycle arrest and inhibition of migration.
- Dual inhibition modulated key proteins involved in cell cycle regulation and metastasis.
Conclusions:
- Dual inhibition of PI3K/Akt and MAPK/ERK pathways represents a potential therapeutic strategy for HSCC.
- The combination of GDC-0980 and Refametinib shows promise for improving treatment outcomes in HSCC patients.
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