A Potential Combination of Targeting HSP90 and mTOR in Breast Cancer Cell Growth, Migration, and Invasion Through Inhibiting AKT Phosphorylation and F-actin Organization

Background/Aim: Breast cancer is the most prevalent cancer among women worldwide, with high mortality primarily due to metastasis. However, there is currently no effective treatment for patients with metastatic disease. This study explores the therapeutic potential of combining HSP90 and mTOR inhibitors to suppress breast cancer cell growth, migration, and invasion.

Materials and Methods: Gene Expression Profiling Interactive Analysis (GEPIA) was used to assess gene expression profiles. Western blot analysis and fluorescence staining were performed to evaluate protein expression and localization. MTT, wound healing, and transwell invasion assays were conducted to assess cell proliferation, migration, and invasion, respectively.

Results: GEPIA analysis revealed significantly higher HSP90 expression in breast invasive carcinoma compared to other tumor types, with a positive correlation to mTOR levels. Treatment with 17-AAG (an HSP90 inhibitor) and Torkinib (an mTORC1/2 inhibitor) significantly reduced cell proliferation. Combination therapy also downregulated AKT signaling and induced morphological changes, including reduced F-actin intensity and decreased nuclear localization of YAP.

Conclusion: Dual inhibition of HSP90 and mTOR suppresses breast cancer progression by disrupting AKT signaling and inhibiting F-actin polymerization. This combination therapy may offer a promising strategy to enhance treatment efficacy while mitigating the limitations of single-agent therapies.