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Ginsenoside Rk1 Enhances Chemosensitivity of Gastric Cancer Through Activating the AMPK/mTOR Pathway
Yaqin Huang1, Jian Wu1, Li Zheng1
1Department of Gastroenterology, The First Hospital of Nanchang, Nanchang, China.
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.
Insights
Ginsenoside Rk1, a compound from ginseng, effectively inhibits gastric cancer (GC) growth and metastasis. It works by activating the AMPK/mTOR pathway, offering a potential new treatment strategy for GC.
Area of Science:
- Oncology
- Pharmacology
- Natural Products
Background:
- Ginseng extracts demonstrate therapeutic potential against gastric cancer (GC).
- Ginsenoside Rk1 (Rk1) is a key compound investigated for its anti-cancer properties.
- Understanding Rk1's mechanisms in GC is crucial for developing novel treatments.
Purpose of the Study:
- To investigate the anti-cancer functions of Ginsenoside Rk1 (Rk1) in gastric cancer (GC).
- To elucidate the underlying molecular mechanisms of Rk1's action on GC cells.
- To evaluate Rk1's efficacy both in vitro and in vivo.
Main Methods:
- Cell viability, proliferation, invasion, migration, and apoptosis were assessed using CCK-8, BrdU, Transwell, and TUNEL assays.
- Gene expression related to apoptosis was analyzed via RT-PCR.
- Western blotting was employed to determine the activation status of the AMPK/mTOR pathway.
- An in vivo tumor xenograft model in nude mice was utilized to evaluate Rk1's effect on tumor growth.
Main Results:
- Rk1 significantly inhibited GC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
- Rk1 promoted apoptosis in GC cells and enhanced their sensitivity to common chemotherapy drugs.
- Mechanistically, Rk1 activated the AMPK/mTOR pathway by increasing AMPK phosphorylation and decreasing mTOR phosphorylation.
- In vivo studies demonstrated that Rk1 markedly suppressed tumor growth and exhibited synergistic effects with cisplatin and oxaliplatin.
Conclusions:
- Ginsenoside Rk1 exhibits significant antitumor activity against gastric cancer.
- The anti-cancer effects of Rk1 are mediated through the activation of the AMPK/mTOR signaling pathway.
- Rk1 represents a promising therapeutic agent for gastric cancer, potentially enhancing chemotherapy efficacy.
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