A novel small molecule LLL12B inhibits STAT3 signaling and sensitizes ovarian cancer cell to paclitaxel and cisplatin
PublisherPublic Library of Science
MetadataShow full item record
AbstractOvarian cancer is the fifth most common cause of cancer deaths among American women. Platinum and taxane combination chemotherapy represents the first-line approach for ovarian cancer, but treatment success is often limited by chemoresistance. Therefore, it is necessary to find new drugs to sensitize ovarian cancer cells to chemotherapy. Persistent activation of Signal Transducer and Activator of Transcription 3 (STAT3) signaling plays an important role in oncogenesis. Using a novel approach called advanced multiple ligand simultaneous docking (AMLSD), we developed a novel nonpeptide small molecule, LLL12B, which targets the STAT3 pathway. In this study, LLL12B inhibited STAT3 phosphorylation (tyrosine 705) and the expression of its downstream targets, which are associated with cancer cell proliferation and survival. We showed that LLL12B also inhibits cell viability, migration, and proliferation in human ovarian cancer cells. LLL12B combined with either paclitaxel or with cisplatin demonstrated synergistic inhibitory effects relative to monotherapy in inhibiting cell viability and LLL12B-paclitaxel or LLL12B-cisplatin combination exhibited greater inhibitory effects than cisplatin-paclitaxel combination in ovarian cancer cells. Furthermore, LLL12B-paclitaxel or LLL12B-cisplatin combination showed more significant in inhibiting cell migration and growth than monotherapy in ovarian cancer cells. In summary, our results support the novel small molecule LLL12B as a potent STAT3 inhibitor in human ovarian cancer cells and suggest that LLL12B in combination with the current front-line chemotherapeutic drugs cisplatin and paclitaxel may represent a promising approach for ovarian cancer therapy.
Ovarian Neoplasms--drug therapy
STAT3 Transcription Factor--antagonists & Inhibitors
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/15599
- A small molecule STAT3 inhibitor, LLL12, enhances cisplatin‑ and paclitaxel‑mediated inhibition of cell growth and migration in human ovarian cancer cells.
- Authors: Zhang R, Chen X, Fu S, Xu L, Lin J
- Issue date: 2020 Sep
- LLL12B, a small molecule STAT3 inhibitor, induces growth arrest, apoptosis, and enhances cisplatin-mediated cytotoxicity in medulloblastoma cells.
- Authors: Chen X, Pan L, Wei J, Zhang R, Yang X, Song J, Bai RY, Fu S, Pierson CR, Finlay JL, Li C, Lin J
- Issue date: 2021 Mar 22
- Inhibition of the JAK2/STAT3 pathway in ovarian cancer results in the loss of cancer stem cell-like characteristics and a reduced tumor burden.
- Authors: Abubaker K, Luwor RB, Zhu H, McNally O, Quinn MA, Burns CJ, Thompson EW, Findlay JK, Ahmed N
- Issue date: 2014 May 6
- STAT3 inhibitor in combination with irradiation significantly inhibits cell viability, cell migration, invasion and tumorsphere growth of human medulloblastoma cells.
- Authors: Pan L, Zhang R, Ma L, Pierson CR, Finlay JL, Li C, Lin J
- Issue date: 2021 Jul 13
- Chemosensitizing effects of metformin on cisplatin- and paclitaxel-resistant ovarian cancer cell lines.
- Authors: Dos Santos Guimarães I, Ladislau-Magescky T, Tessarollo NG, Dos Santos DZ, Gimba ERP, Sternberg C, Silva IV, Rangel LBA
- Issue date: 2018 Jun