Triptolide Inhibits Lung Cancer Cell Migration, Invasion, and Metastasis
Theresa A Reno1, Jae Y Kim1, Dan J Raz1
1Division of Thoracic Surgery, City of Hope Medical Center, Duarte, California.
Background:
Triptolide is an extract from Tripterygium wilfordii used in traditional Chinese medicine to treat autoimmune disorders. Triptolide has anticancer effects in vitro and is reported to impair cancer cell migration. We studied whether triptolide inhibits lung cancer cell migration and metastasis.
Methods:
We determined the microRNA expression profile of triptolide-treated cells. We tested the effects of triptolide treatment on migration and invasion of lung cancer cells by using Transwell filters coated with fibronectin and Matrigel, respectively. Western blot analyses were used to compare expression of proteins involved in cell migration before and after 10 nmol/L triptolide treatment. Tail vein injections with H358 cells were performed. The mice were treated with 1 mg/kg triptolide or vehicle by intraperitoneal injection three times per week. Lung and liver metastases were compared at 9 weeks. Means of groups were compared by using a t test.
Results:
Triptolide altered the expression of microRNAs involved in cellular movement and significantly decreased migration and invasion of lung cancer cells from approximately 18 to 3 cells per field (p < 0.001). Triptolide decreases focal adhesion kinase expression, which leads to impairment of downstream signaling. Finally, triptolide-treated mice injected with lung cancer cells significantly decreased metastatic colony formation in the lungs (p < 0.01).
Conclusions:
Triptolide decreases lung cancer cell migration and invasion in vitro and inhibits metastatic tumor formation in mice. Triptolide suppresses focal adhesion kinase, which causes deregulation of the migration machinery. These results suggest that triptolide inhibits lung cancer metastasis and should be investigated as a new lung cancer therapy.
Insights
Triptolide, a traditional Chinese medicine extract, significantly inhibits lung cancer cell migration and invasion in vitro and reduces metastasis in mice. It suppresses focal adhesion kinase, suggesting potential as a novel lung cancer therapy.
Area of Science:
- Pharmacology
- Oncology
- Molecular Biology
Background:
- Triptolide, derived from Tripterygium wilfordii, is used in traditional Chinese medicine for autoimmune disorders.
- Triptolide exhibits in vitro anticancer effects and is known to impede cancer cell migration.
Purpose of the Study:
- To investigate the inhibitory effects of triptolide on lung cancer cell migration and metastasis.
- To elucidate the molecular mechanisms underlying triptolide's anti-migratory and anti-metastatic actions in lung cancer.
Main Methods:
- Assessed microRNA expression profiles in triptolide-treated lung cancer cells.
- Utilized Transwell assays to evaluate the impact of triptolide on cell migration and invasion.
- Performed Western blot analysis to examine protein expression changes, focusing on focal adhesion kinase.
- Evaluated triptolide's efficacy in reducing lung and liver metastases in a mouse model via tail vein injection.
Main Results:
- Triptolide significantly reduced lung cancer cell migration and invasion in vitro (approx. 18 to 3 cells/field, p < 0.001).
- Triptolide treatment led to decreased expression of focal adhesion kinase, impairing downstream signaling pathways.
- Triptolide administration significantly inhibited metastatic colony formation in the lungs of treated mice (p < 0.01).
Conclusions:
- Triptolide effectively inhibits lung cancer cell migration and invasion in vitro and suppresses tumor metastasis in vivo.
- The mechanism involves the suppression of focal adhesion kinase, leading to the deregulation of the cell migration machinery.
- These findings highlight triptolide as a promising candidate for further investigation as a novel therapeutic agent for lung cancer treatment.
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