A Potential Combination of Targeting HSP90 and mTOR in Breast Cancer Cell Growth, Migration, and Invasion Through Inhibiting AKT Phosphorylation and F-actin Organization
Breast cancer is the most common cancer among women worldwide and has a high death rate, mainly due to metastasis. Unfortunately, no effective treatment is available for metastatic breast cancer. The potential of combining HSP90 and mTOR inhibitors to treat breast cancer cell growth, migration, and invasion was explored in this study. Gene expression profiles were examined using Gene Expression Profiling Interactive Analysis (GEPIA).
Protein expression and localization were studied using Western blot analysis and fluorescence staining. Cell proliferation, migration, and invasion were assessed using MTT, wound healing, and transwell invasion assays. It was found that HSP90 expression was significantly higher in breast invasive carcinoma compared to other tumor types, and this high expression was linked to mTOR levels. Cell proliferation was significantly inhibited by treatment with 17-AAG (an HSP90 inhibitor) and Torkinib (an mTORC1/2 inhibitor). AKT signaling was reduced, F-actin intensity was decreased, and YAP levels were lowered by the combination treatment, disrupting its nuclear localization.
In conclusion, breast cancer cell growth and progression can be suppressed by targeting HSP90 and mTOR, which interferes with AKT signaling and inhibits F-actin polymerization. This combination treatment shows promise as a therapeutic strategy for breast cancer, potentially reducing the adverse effects of single treatments.
![](https://pathobiology.sc.mahidol.ac.th/wp-content/uploads/2025/01/A-Potential-e1738312180456.png)