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Published on: October 27, 2020
Ginsenoside Rd attenuates breast cancer metastasis implicating derepressing microRNA-18a-regulated Smad2 expression
Peiwei Wang1, Xiaoye Du1, Minqi Xiong1
1Yueyang Hospital &Clinical Research Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
Abstract:
Metastasis remains a major cause of mortality and poor prognosis in breast cancer patients. Anti-metastatic therapies are in great need to achieve optimal clinical outcome in breast cancer patients. Panax Notoginseng Saponins (PNS) has previously been shown to inhibit breast cancer metastasis in mouse. Here the potential anti-metastatic effect of one of the chemical compounds of PNS, ginsenoside Rd (Rd), was further evaluated in mouse mammary carcinoma 4T1 cells. The results revealed that Rd treatment dose-dependently suppressed cell migration and invasion in cultured 4T1 cells. In 4T1 cell-inoculated mice, Rd treatment led to decreased number of tumor lesions in lungs in both spontaneous and experimental metastasis models. Rd treatment resulted in increased expression of Smad2 in cultured 4T1 cells and in tumors grown from inoculated 4T1 cells. Rd treatment decreased the expression of microRNA (miR)-18a in cultured 4T1 cells and in tumors derived from inoculated 4T1 cells. Smad2 was further verified to be a direct target of miR-18a in 4T1 cells. The significant impact of Rd on counteracting miR-18a-medidated downregulation of Smad2 expression was also demonstrated. Together, the current work shows for the first time that Rd treatment attenuates breast cancer metastasis in part through derepressing miR-18a-mediated Smad2 expression regulation.
Insights
Ginsenoside Rd (Rd) effectively suppresses breast cancer metastasis by regulating miR-18a and Smad2 expression. This natural compound offers a promising avenue for developing novel anti-metastatic therapies.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Metastasis is a primary driver of breast cancer mortality, necessitating the development of effective anti-metastatic therapies.
- Panax Notoginseng Saponins (PNS) have demonstrated anti-metastatic properties in preclinical models.
- Ginsenoside Rd (Rd), a key component of PNS, warrants investigation for its specific anti-metastatic potential.
Purpose of the Study:
- To evaluate the anti-metastatic effects of ginsenoside Rd (Rd) in breast cancer.
- To elucidate the molecular mechanisms underlying Rd's anti-metastatic action, focusing on miR-18a and Smad2 signaling.
Main Methods:
- In vitro studies using 4T1 mouse mammary carcinoma cells to assess cell migration and invasion.
- In vivo studies using 4T1 cell inoculation models (spontaneous and experimental metastasis) in mice to evaluate lung metastasis.
- Molecular analyses including Western blotting and microRNA expression profiling to determine the impact of Rd on Smad2 and miR-18a levels.
Main Results:
- Rd treatment dose-dependently inhibited 4T1 cell migration and invasion in vitro.
- Rd significantly reduced lung metastasis in both spontaneous and experimental metastasis mouse models.
- Rd increased Smad2 expression and decreased miR-18a expression in 4T1 cells and tumors.
- Smad2 was identified as a direct target of miR-18a, and Rd counteracted miR-18a-mediated Smad2 downregulation.
Conclusions:
- Ginsenoside Rd exhibits significant anti-metastatic effects in breast cancer models.
- Rd attenuates breast cancer metastasis by modulating the miR-18a/Smad2 pathway.
- Rd represents a potential therapeutic agent for combating breast cancer metastasis.
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