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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Li, Yi Dong, Yuyan |
| Abstract | Background Cervical cancer (CC) is a significant global health concern, demanding the consideration of novel therapeutic strategies. The signal transducer and activator of transcription 3 (STAT3) pathway has been implicated in cancer progression and is a potential target for therapeutic intervention. This study aimed to explore the therapeutic potential of TTI-101, a small molecule STAT3 inhibitor, in CC and investigate its underlying mechanisms. Methods Molecular docking studies and molecular dynamics simulations were performed to explore the binding interaction between TTI-101 and STAT3 and assess the stability of the STAT3-TTI-101 complex. Cell viability assays, wound healing assays, colony formation assays, flow cytometry analysis, and gene expression analysis were conducted. In vivo xenograft models were used to assess the antitumor efficacy of TTI-101. Results The in silico analysis shows a stable binding interaction between TTI-101 and STAT3. TTI-101 treatment inhibits cell viability, clonogenic ability, and cell migration in CC cells. Furthermore, TTI-101 induces apoptosis and cell cycle arrest. Analysis of apoptosis-related markers demonstrated dysregulation of Bax, Bcl-2, and Caspase-3 upon TTI-101 treatment. Moreover, TTI-101 caused G2/M phase arrest accompanied by a decrease in CDK1 and Cyclin B1 at mRNA levels. In the xenograft model, TTI-101 significantly inhibited tumor growth without adverse effects on body weight. Conclusion TTI-101 exhibited anticancer effects by targeting the STAT3/c-Myc signaling pathway, inducing cell cycle arrest, and promoting apoptosis in CC cells. These findings provide valuable insights into the development of novel therapeutic strategies for cervical cancer. Further investigation is warranted to validate the clinical application of TTI-101. Graphical Abstract |
| Related Links | https://cancerci.biomedcentral.com/counter/pdf/10.1186/s12935-024-03463-6.pdf |
| Ending Page | 14 |
| Page Count | 14 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14752867 |
| DOI | 10.1186/s12935-024-03463-6 |
| Journal | Cancer Cell International |
| Issue Number | 1 |
| Volume Number | 24 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-08-12 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Cell Biology Cervical cancer TTI-101 Signal transducer and activator of transcription 3 (STAT3) Cell cycle arrest STAT3 inhibitor |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Genetics Oncology |
| Journal Impact Factor | 5.3/2023 |
| 5-Year Journal Impact Factor | 5/2023 |
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