Abstract
Signal transducer and activator of transcription 3 (STAT3) modulates a variety of genes involved in the regulation of critical functions, including cell proliferation, differentiation, apoptosis, angiogenesis, metastasis, and immunity. For many cancers, elevated levels of STAT3 signaling have been associated with a poor prognosis and the development of chemotherapy resistance. In this study, we investigated the inhibitory effects of a novel small-molecule inhibitor of STAT3, STX-0119, on the cell viability and survival of human lung cancer cells. STX-0119 inhibited activated STAT3 and the expression of STAT3-regulated oncoproteins such as c-Myc, cyclin D1, and survivin in lung cancer cells. STX-0119 also decreased the amount of STAT3 in the nuclear fraction as well as induced apoptosis of these lung cancer cell lines as evidenced by increases in apoptotic cells (Annexin V positive) and poly (ADP-ribose) polymerase (PARP) cleavage. The efficacy of STX-0119 in a mouse xenograft model was confirmed. However, a hematological side effect, which had not been previously reported, was observed. The level of white blood cells was significantly lowered when treated at the dose at which STX-0119 alone showed a significant tumor-suppressive effect. In conclusion, we suggest that STX-0119 may be a potent therapeutic agent against lung cancer. Consideration of the side effect suggests, it is necessary to study whether low-dose STX-0119 is effective for lung treatment with a combination of classic lung cancer therapeutics.
Highlights
The signal transducer and activator of transcription (STAT) family of proteins is a group of transcription factors that regulate gene expression related to the cell cycle, cell survival, and the immune response
Western blotting analysis of lysate from lung cancer cells treated with STX-0119 showed that STX0119 decreased the expression of Signal transducer and activator of transcription 3 (STAT3) target proteins such as c-Myc, cyclin D1, and survivin in a concentration-dependent manner (Fig. 1c)
STX-0119 inhibits viability and clonogenic ability of lung cancer cells To test whether STX-0119 affects cell viability, we measured the proliferation of lung cancer cells after STX0119 treatment by performing MTT assays
Summary
The signal transducer and activator of transcription (STAT) family of proteins is a group of transcription factors that regulate gene expression related to the cell cycle, cell survival, and the immune response. STAT3 has been reported to be involved in oncogenesis by up-regulating the transcription of several genes that control primary tumor cell survival, resistance to apoptosis, cell cycle activation, and angiogenesis [4,5,6,7]. Dysregulated STAT3 activity is involved in hematologic malignancies, head and neck cancers, and leukemia and has been implicated in the pathogenesis of a subset of solid tumors [9,10,11]. There have been reports that STAT3 activation maintains cancer stem cell phenotypes, facilitating drug resistance and tumor recurrence [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
