Introduction to Nanoparticle-Based Therapy for Triple-Negative Breast Cancer
Tia Harmon and Dr. Ruben Gonzalez-Perez from the Morehouse School of Medicine and Emory University utilized the imaging and analysis capabilities of the Cellometer Vision to investigate leptin peptide receptor antagonist-conjugated nanoparticles in order to inhibit leptin signaling, a key pathway that promotes growth and survival of triple-negative breast cancer (TNBC) cells. It was hypothesized that these nanoparticles would first stop the expression of leptin’s downstream target Notch, and would thereby increase the effectiveness of standard chemotherapeutic compounds in limiting tumor cell survival [1-4].
Materials and Methods
A human ER+ cell line (MCF-7) and TNBC cell line HCC1806 were cultured and exposed to various concentrations of sunitinib (SUT), paclitaxel (PTX), and doxorubicin (DOX), both alone (data not shown) and in combination with the leptin peptide receptor antagonist-conjugated nanoparticles (IONP-LPrA2). The Cellometer Vision CBA imaged and analyzed all samples for apoptosis as well as cell cycle in response to the various treatments.
HCC1806 cells were also treated with leptin alone or leptin plus IONP-LPrA2 for 24 hours before incubation with anti-Notch1, which the Cellometer Vision CBA used to evaluate Notch expression in those cultures.
- In combination with each of four chemotherapeutic agents, IONP-LPrA2 decreased cell survival when compared to the chemotherapeutic agent alone in both ER+ and TNBC cell cultures.
- Treating HCC1806 cells with leptin increased Notch expression.
- Treating HCC1806 cells with leptin plus ION-LPrA2 abrogated leptin’s effect on Notch expression.
ION-LPrA2 has potential to be a novel adjuvant therapy in breast cancer, specifically in the cases of the more difficult to treat TNBC.
*Note: the poster presentation outlining these experiments in more detail may be found here http://www.ejcancer.com/article/S0959-8049(14)70393-4/abstract
- Gonzalez, R.R. and P.C. Leavis, A peptide derived from the human leptin molecule is a potent inhibitor of the leptin receptor function in rabbit endometrial cells. Endocrine, 2003. 21(2): p. 185-95.
- Yang, L., et al., Receptor-targeted nanoparticles for in vivo imaging of breast cancer. Clin Cancer Res, 2009. 15(14): p. 4722-32.
- Guo, S., et al., Oncogenic role and therapeutic target of leptin signaling in breast cancer and cancer stem cells. Biochim Biophys Acta, 2012. 1825(2): p. 207-22.
- Schneiderman, R.S., et al., TTFields alone and in combination with chemotherapeutic agents effectively reduce the viability of MDR cell sub-lines that over-express ABC transporters. BMC Cancer, 2010. 10: p. 229.