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Mitigation of Breast Cancer Cells' Invasiveness via Down Regulation of ETV7, Hippo, and PI3K/mTOR Pathways by Vitamin
1Mechanical Engineering Department, Texas Tech University, Lubbock, TX 79409, USA.
Abstract:
Metastasis in breast cancer is the major cause of death in females (about 30%). Based on our earlier observation that Vitamin D3 downregulates mTOR, we hypothesized that Vitamin D3 conjugated to gold nanoparticles (VD3-GNPs) reduces breast cancer aggressiveness by downregulating the key cancer controller PI3K/AKT/mTOR. Western blots, migration/invasion assays, and other cell-based, biophysical, and bioinformatics studies are used to study breast cancer cell aggressiveness and nanoparticle characterization. Our VD3-GNP treatment of breast cancer cells (MCF-7 and MDA-MB-231) significantly reduces the aggressiveness (cancer cell migration and invasion rates > 45%) via the simultaneous downregulation of ETV7 and the Hippo pathway. Consistent with our hypothesis, we, indeed, found a downregulation of the PI3K/AKT/mTOR pathway. It is surprising that the extremely low dose of VD3 in the nano formulation (three orders of magnitude lower than in earlier studies) is quite effective in the alteration of cancer invasiveness and cell signaling pathways. Clearly, VD3-GNPs are a viable candidate for non-toxic, low-cost treatment for reducing breast cancer aggressiveness.
Insights
Vitamin D3 conjugated to gold nanoparticles (VD3-GNPs) effectively reduces breast cancer aggressiveness by downregulating key signaling pathways. This novel nano formulation shows promise for non-toxic, low-cost breast cancer treatment.
Area of Science:
- Oncology
- Nanotechnology
- Biochemistry
Background:
- Metastasis is the primary cause of death in breast cancer patients.
- Vitamin D3 has been observed to downregulate the mTOR pathway.
- Targeting the PI3K/AKT/mTOR pathway is crucial for controlling cancer aggressiveness.
Purpose of the Study:
- To investigate if Vitamin D3-conjugated gold nanoparticles (VD3-GNPs) can reduce breast cancer aggressiveness.
- To determine if VD3-GNPs downregulate the PI3K/AKT/mTOR pathway in breast cancer cells.
- To explore the efficacy of a low-dose nano formulation of Vitamin D3.
Main Methods:
- Utilized Western blots to analyze protein expression.
- Performed migration and invasion assays to assess cancer cell aggressiveness.
- Conducted cell-based, biophysical, and bioinformatics studies for comprehensive analysis.
- Characterized the synthesized VD3-GNPs.
Main Results:
- VD3-GNP treatment significantly reduced breast cancer cell migration and invasion rates by over 45%.
- Observed simultaneous downregulation of ETV7 and the Hippo pathway.
- Confirmed the downregulation of the PI3K/AKT/mTOR pathway, consistent with the hypothesis.
- Demonstrated the effectiveness of an extremely low dose of VD3 in the nano formulation.
Conclusions:
- VD3-GNPs are a promising candidate for reducing breast cancer aggressiveness.
- The nano formulation is effective at significantly lower doses compared to previous studies.
- VD3-GNPs offer a potential non-toxic and low-cost therapeutic strategy for breast cancer.
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