Gomisin A enhances the antitumor effect of paclitaxel by suppressing oxidative stress in ovarian cancer

Oncol Rep. 2022 Nov;48(5):202. doi: 10.3892/or.2022.8417. Epub 2022 Sep 28.

Abstract

Gomisin A (GA) is an effective component of Schisandra. The crude extracts of Schisandra chinensis and its active ingredients have been shown to inhibit multidrug resistance in tumour cells. Reactive oxygen species (ROS) have different roles in cancer and may contribute to therapy resistance. The human ovarian cancer (OC) cell lines SKOV3 and A2780, and a mouse model of OC, were used in the present study. MTT assay, colony formation assay, flow cytometry, western blot analysis, and haematoxylin and eosin (H&E) staining were performed to determine the antitumor effect of GA and paclitaxel (PTX) in vitro and in vivo. The ROS inhibitor N‑acetyl cysteine (NAC) was used to assess the mechanism underlying the chemosensitizing effects of GA. Notably, the proliferation of OC cells was inhibited by PTX, which could be enhanced by the ROS inhibitor NAC or GA. Treatment with NAC + PTX or GA + PTX enhanced the cell cycle arrest, but not apoptosis, induced by PTX. Moreover, the molecular mechanism underlying this effect may be that GA decreases the levels of ROS in ovarian cancer cells and inhibits cell cycle progression by downregulating the expression of the cell cycle proteins cyclin‑dependent kinase 4 and cyclin B1. In conclusion, the combination of PTX and the ROS inhibitor GA may be a novel strategy in OC chemotherapy.

Keywords: GA; OC; PTX; ROS; chemosensitization.

MeSH terms

  • Animals
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Cell Proliferation
  • Complex Mixtures / pharmacology
  • Cyclin B1 / metabolism
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclooctanes
  • Cysteine / pharmacology
  • Dioxoles
  • Eosine Yellowish-(YS) / pharmacology
  • Eosine Yellowish-(YS) / therapeutic use
  • Female
  • Humans
  • Lignans
  • Mice
  • Ovarian Neoplasms* / pathology
  • Oxidative Stress
  • Paclitaxel* / pharmacology
  • Paclitaxel* / therapeutic use
  • Reactive Oxygen Species / metabolism

Substances

  • Complex Mixtures
  • Cyclin B1
  • Cyclooctanes
  • Dioxoles
  • Lignans
  • Reactive Oxygen Species
  • schizandrol B
  • Cyclin-Dependent Kinase 4
  • Cysteine
  • Paclitaxel
  • Eosine Yellowish-(YS)

Grants and funding

This work was supported by grants from the Jilin Province of Department Finance (grant nos. 2019SCZT040 and 2019SCZT050) and the Jilin Province Science and Technology Department (grant no. 20200201589JC).