Discipline: Biological Sciences
Subcategory: Cancer Research
Waynesha Blaylock - Tougaloo College
Co-Author(s): Petra den Hollander, Abhijit Mazumdar, and Powel H. Brown, University of Texas MD Anderson Cancer Center, Houston, TX
Breast cancer, the most common cancer among women in the United States, is the second leading cause of cancer-related deaths in women. It is estimated that in 2015, about 40,290 women in the U.S. will die from breast cancer. Clinically, breast tumors can be categorized as Estrogen receptor positive (ER+), human epidermal growth factor receptor 2 (Her2+), or triplenegative breast cancer (TNBC) (ER-, Her2-, and PR-). ER+ and Her2+ breast cancers can be successfully treated with targeted therapies. However, TNBCs have a poor prognosis and chemotherapy is currently the only treatment option. With the lack of targeted treatment for certain types of breast tumors, there is a high necessity for the identification of targets and the development of drugs that can treat these types of breast cancers. One of these targets is signal transducer and activator of transcription 3 (STAT3). STAT3 is a protein that is upregulated in breast cancer compared to normal tissue, and is reported to be constitutively activated in 50-60% of breast tumors. Phosphorylated and activated STAT3 homodimers translocate into the nucleus where they induce gene transcription. The objective of this research was to test a novel STAT3 inhibitor (Compound 188) on various human and mouse breast carcinoma cell lines to determine the effect on breast cancer cell growth. The hypothesis stated that inhibition of the STAT3 transcription factor using a small molecule inhibitor will inhibit STAT3 signaling and suppress breast cancer cell growth. A set of nine breast cancer cell lines were treated with the STAT3 inhibitor or vehicle. The controls for this research were the ER+ breast cancer cell lines. Growth assays, western blots, and RTqPCR were performed to test the effect of the drugs on the various cell lines. The results showed that compound 188 reduced cell growth in one-half of the human breast carcinoma cell lines and one-third of the mouse mammary carcinoma cell lines. Compound 188 inhibited phosphorylation of STAT3 and reduced the amount of total STAT3 present in cells. The STAT3 inhibitor induced p21, BCL-2, and c-Myc mRNA levels in T-47D cells, but had no effect on the mRNA levels of Survivin. Compound 188 could be used as a cancer therapy agent for the treatment of breast cancer. Compound 188 could also be used for the treatment of other cancers dependent on the STAT3 signaling pathway.
References: Chung, Seyung S. et al. ‘STAT3 activation in HER2overexpressing breast cancer promotes epithelial-mesenchymal transition and cancer stem cell traits.’ International Journal of Oncology 44.2 (2014): 403-411. 1.
Xu, Xuejun et al. “Chemical Probes that Competitively and Selectively Inhibit Stat3 Activation.” PLoS ONE 4.3 (2009): e4783.
Funder Acknowledgement(s): This research was supported, in part, by University of Texas MD Anderson Cancer Center's CPRIT -CURE Summer Program. Additional support was provided by the Susan G. Koman for the Cure Promise Grant awarded to Powel H. Brown, MD, PhD, Chair, Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Faculty Advisor: Powel H. Brown,