1. Academic Validation
  2. A small molecule STAT3 inhibitor, LLL12, enhances cisplatin‑ and paclitaxel‑mediated inhibition of cell growth and migration in human ovarian cancer cells

A small molecule STAT3 inhibitor, LLL12, enhances cisplatin‑ and paclitaxel‑mediated inhibition of cell growth and migration in human ovarian cancer cells

  • Oncol Rep. 2020 Sep;44(3):1224-1232. doi: 10.3892/or.2020.7667.
Ruijie Zhang 1 Xiang Chen 2 Shengling Fu 1 Liang Xu 3 Jiayuh Lin 2
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
  • 2 Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
  • 3 Department of Molecular Biosciences, University of Kansas Medical School, University of Kansas, Lawrence, KS 66045, USA.
Abstract

Ovarian Cancer is one of the most lethal Cancer types in American women. The platinum agent cisplatin, and/or paclitaxel, remains the first‑line chemotherapy for ovarian Cancer, but the treatment success is severely limited by chemoresistance. As previously reported, persistent STAT3 signaling is associated with resistance to cisplatin and paclitaxel. To investigate whether the STAT3 small molecule inhibitor LLL12 can enhance the treatment effect of cisplatin and paclitaxel in ovarian Cancer cells, A2780, SKOV3, CAOV‑3 and OVCAR5 cells were treated with LLL12, cisplatin and paclitaxel, alone or combination, and cell viability, cell migration, cell growth and protein expression levels were then evaluated. It was found that, for all four human ovarian Cancer cell lines, STAT3 phosphorylation was significantly inhibited by LLL12. The combined treatment of LLL12 with paclitaxel or LLL12 with cisplatin exerted significantly greater inhibition of cell viability, cell migration and cell growth than did monotherapy. In addition, LLL12 and cisplatin in combination, or the three drugs in combination, also led to greater inhibition of cell viability and cell migration than combined cisplatin and paclitaxel treatment, a standard treatment for ovarian Cancer. The present results demonstrated that the STAT3 small molecule inhibitor LLL12 is a potent inhibitor of STAT3 phosphorylation, cell viability and migration in human ovarian Cancer cells. Combining LLL12 with cisplatin or paclitaxel may be a viable therapeutic approach in the treatment of patients with ovarian Cancer exhibiting persistent STAT3 signaling.

Keywords

STAT3; ovarian cancer; small molecule inhibitors.

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