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Cardamonin Inhibits Metastasis of Lewis Lung Carcinoma Cells by Decreasing mTOR Activity
Pei-Guang Niu1, Yu-Xuan Zhang1, Dao-Hua Shi1
1Department of Pharmacy, Fujian Provincial Maternal and Child Health Hospital, Fuzhou, Fujian, China.
Abstract:
The mammalian target of rapamycin (mTOR) regulates the motility and invasion of cancer cells. Cardamonin is a chalcone that exhibits anti-tumor activity. The previous study had proved that the anti-tumor effect of cardamonin was associated with mTOR inhibition. In the present study, the anti-metastatic effect of cardamonin and its underlying molecule mechanisms were investigated on the highly metastatic Lewis lung carcinoma (LLC) cells. The proliferation, invasion and migration of LLC cells were measured by MTT, transwell and wound healing assays, respectively. The expression and activation of mTOR- and adhesion-related proteins were assessed by Western blotting. The in vivo effect of cardamonin on the metastasis of the LLC cells was investigated by a mouse model. Treated with cardamonin, the proliferation, invasion and migration of LLC cells were significantly inhibited. The expression of Snail was decreased by cardamonin, while that of E-cadherin was increased. In addition, cardamonin inhibited the activation of mTOR and its downstream target ribosomal S6 kinase 1 (S6K1). Furthermore, the tumor growth and its lung metastasis were inhibited by cardamonin in C57BL/6 mice. It indicated that cardamonin inhibited the invasion and metastasis of LLC cells through inhibiting mTOR. The metastasis inhibitory effect of cardamonin was correlated with down-regulation of Snail and up-regulation of E-cadherin.
Insights
Cardamonin, a natural compound, effectively inhibits cancer cell invasion and metastasis by targeting the mammalian target of rapamycin (mTOR) pathway. This study demonstrates cardamonin
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Mammalian target of rapamycin (mTOR) pathway is crucial for cancer cell motility and invasion.
- Cardamonin, a chalcone, possesses anti-tumor properties linked to mTOR inhibition.
- Lewis lung carcinoma (LLC) cells are a model for highly metastatic cancer.
Purpose of the Study:
- To investigate the anti-metastatic effects of cardamonin on LLC cells.
- To elucidate the molecular mechanisms underlying cardamonin's anti-metastatic action.
- To evaluate the in vivo efficacy of cardamonin against LLC metastasis.
Main Methods:
- Cell proliferation, invasion, and migration assays (MTT, Transwell, Wound Healing).
- Western blotting to assess mTOR pathway and adhesion-related protein expression/activation.
- In vivo mouse model (C57BL/6) to study metastasis and tumor growth.
Main Results:
- Cardamonin significantly inhibited LLC cell proliferation, invasion, and migration.
- Cardamonin treatment led to decreased Snail expression and increased E-cadherin expression.
- Cardamonin suppressed mTOR activation and its downstream target S6K1.
- In vivo, cardamonin reduced tumor growth and lung metastasis in mice.
Conclusions:
- Cardamonin exhibits anti-metastatic effects on Lewis lung carcinoma cells by inhibiting the mTOR pathway.
- The anti-metastatic mechanism involves down-regulation of Snail and up-regulation of E-cadherin.
- Cardamonin shows therapeutic potential for inhibiting cancer metastasis.
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