Notoginsenoside R1 attenuates breast cancer progression by targeting CCND2 and YBX3

Chin Med J (Engl). 2021 Jan 20;134(5):546-554. doi: 10.1097/CM9.0000000000001328.

Abstract

Background: Breast cancer (BC) is a common malignancy with highly female incidence. So far the function of notoginsenoside R1 (NGR1), the extract from Panax notoginseng, has not been clearly elucidated in BC.

Methods: Optimal culture concentration and time of NGR1 were investigated by cell counting kit-8 assay. Cell proliferation ability was measured by colony formation assays. Transwell assay was used to detect the effect of NGR1 on cell migration and invasion. The apoptosis rate of cells between each group was measured by TUNEL assay.

Results: NGR1 treatment has an inhibitory effect on proliferation, migration, invasion, and angiogenesis and a stimulating effect on cell cycle arrest and apoptosis of Michigan Cancer Foundation-7 (MCF-7) cells. The 50% growth inhibitory concentration for MCF-7 cells at 24 h was 148.9 mmol/L. The proportions of MCF-7 cells arrested in the G0/G1 phase were 36.94±6.78%, 45.06±5.60%, and 59.46±5.60% in the control group, 75, and 150 mmol/L groups, respectively. Furthermore, we revealed that NGR1 treatment attenuates BC progression by targeted downregulating CCND2 and YBX3 genes. Additionally, YBX3 activates phosphatidylinositol 3-phosphate kinase (PI3K)/protein kinase B (Akt) signaling pathway by activating kirsten rat sarcoma viral oncogene, which is an activator of the PI3K/Akt signaling pathway.

Conclusion: These results suggest that NGR1 can act as an efficacious drug candidate that targets the YBX3/PI3K/Akt axis in patients with BC.

MeSH terms

  • Animals
  • Apoptosis
  • Breast Neoplasms* / drug therapy
  • Cell Proliferation
  • Cyclin D2
  • Female
  • Ginsenosides* / pharmacology
  • Ginsenosides* / therapeutic use
  • Humans
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Rats

Substances

  • CCND2 protein, human
  • Ccnd2 protein, rat
  • Cyclin D2
  • Ginsenosides
  • Proto-Oncogene Proteins c-akt
  • notoginsenoside R1