Theresa A Reno1, Jae Y Kim1, Dan J Raz2. 1. Division of Thoracic Surgery, City of Hope Medical Center, Duarte, California. 2. Division of Thoracic Surgery, City of Hope Medical Center, Duarte, California. Electronic address: draz@coh.org.
Abstract
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.
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:Triptolidedecreases 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.
Authors: Miguel A Cabrita; Laura M Jones; Jennifer L Quizi; Luc A Sabourin; Bruce C McKay; Christina L Addison Journal: Mol Oncol Date: 2011-10-20 Impact factor: 6.603
Authors: Flavia Pichiorri; Sung-Suk Suh; Alberto Rocci; Luciana De Luca; Cristian Taccioli; Ramasamy Santhanam; Wenchao Zhou; Don M Benson; Craig Hofmainster; Hansjuerg Alder; Michela Garofalo; Gianpiero Di Leva; Stefano Volinia; Huey-Jen Lin; Danilo Perrotti; Michael Kuehl; Rami I Aqeilan; Antonio Palumbo; Carlo M Croce Journal: Cancer Cell Date: 2010-10-19 Impact factor: 31.743
Authors: Isaac Nardi; Theresa Reno; Xinwei Yun; Terra Sztain; Jami Wang; Huifang Dai; Li Zheng; Binghui Shen; Jae Kim; Dan Raz Journal: Int J Cancer Date: 2018-09-19 Impact factor: 7.396
Authors: Catarina Albuquerque; Rita Manguinhas; João G Costa; Nuno Gil; Jordi Codony-Servat; Matilde Castro; Joana P Miranda; Ana S Fernandes; Rafael Rosell; Nuno G Oliveira Journal: Transl Lung Cancer Res Date: 2021-06