Discipline: Biological Sciences
Subcategory: Cancer Research
Justine Lewis - Howard University
Co-Author(s): Lara Brambilla and David Levy, New York University, New York, NY
Signal transducers and activators of transcription (STAT) are latent transcription factors activated by tyrosine phosphorylation. Activated STAT3 promotes cell proliferation and survival and has been implicated in human cancer. Because dysregulated STAT3 contributes to cancer initiation and progression, its inhibition is a promising therapeutic approach. OPB-51602, a small molecule direct inhibitor of STAT3, blocks multiple STAT3 functions. Previous experiments showed that OPB-51602 inhibits growth and survival of tumor cells in a STAT3 dependent manner by targeting mitochondrial STAT3 functions. In this study, we confirm and extend these findings by testing the role of STAT3 in five different human cancer cell lines: Lung Carcinoma (A549), Osteosarcoma (143B), and three types of Melanoma (Mel147, A375 and 451LU). STAT3 was depleted in each cell line by RNA interference, allowing comparison of cell growth in the presence (WT) or absence (KD) of STAT3. We investigated the role of STAT3 in adherent 2-dimensional cultures and assessed the toxicity of OPB-51602 in cells with and without STAT3. Considering previous results, we hypothesize that depleting STAT3 will protect cells from the inhibitory effects of OPB-51602. In four cell lines out of five, STAT3 has no effect on cell growth but in 451LU, higher levels of STAT3 positively affected cell growth (WT grows faster). OPB-51602 affected 3/5 cell lines in a STAT3-dependent manner (in A549, A375, 451LU WT is more sensitive) and affected both WT & KD equally in 143B and Mel147. These data will provide a better understanding of the role of STAT3 in cancer cell growth and the specificity of OPB-51602, and they will contribute to the further development of therapeutic approaches to targeting STAT3 in cancer.
Funder Acknowledgement(s): NIH
Faculty Advisor: David Levy, firstname.lastname@example.org
Role: I conducted all in vitro experiments, except the creation of the knock-down cell lines.