Ginsenoside Rk1 Enhances Chemosensitivity of Gastric Cancer Through Activating the AMPK/mTOR Pathway.

Abstract

Objectives: Ginseng and its extracts have shown promising therapeutic effects on gastric cancer (GC). We aimed to investigate the functions and potential mechanisms of Ginsenoside Rk1 (Rk1) on GC.

Methods: GC cell lines were treated with different doses of Rk1. The CCK-8 assay and BrdU assay were used to measure cell viability and proliferation. A Transwell assay was used to evaluate cell invasion and migration. A TUNEL assay was used to assess cell apoptosis. RT-PCR was conducted to detect apoptosis-associated genes. Western blotting was used to determine the activation of the AMPK/mTOR pathway. An in vivo tumor-bearing nude mouse model was generated to investigate the impact of Rk1 on tumor growth.

Results: Rk1 inhibited the proliferation, migration, invasion, and EMT of GC cells and promoted cell apoptosis. It also enhances the sensitivity of GC cells to chemotherapy drugs (including 5-fluorouracil, vincristine, cisplatin, and oxaliplatin). Mechanistically, Rk1 increased AMPK phosphorylation and repressed mTOR phosphorylation. AMPK inhibition strongly decreased the inhibitory effect of Rk1 on GC cells. In-vivo assays suggested that Rk1 considerably hindered GC growth and had synergistic effects when combined with cisplatin or oxaliplatin.

Conclusion: Ginsenoside Rk1 exerts an antitumor effect on GC by activating the AMPK/mTOR pathway.