Theresa A. Reno, PhD, Jae Y. Kim, MD, Dan J. Raz, MD

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Presentation transcript:

Triptolide Inhibits Lung Cancer Cell Migration, Invasion, and Metastasis Theresa A. Reno, PhD, Jae Y. Kim, MD, Dan J. Raz, MD The Annals of Thoracic Surgery Volume 100, Issue 5, Pages 1817-1825 (November 2015) DOI: 10.1016/j.athoracsur.2015.05.074 Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 Triptolide alters the microRNA (miRNA) expression profile of human lung cancer cells. (A) Heatmap representing the significantly upregulated and downregulated miRNAs after 48 hours of treatment with 10 nmol/L triptolide in H460 human non-small cell lung cancer (NSCLC) cells. (B) Ingenuity Pathway Analysis of the top altered cellular and molecular functions of the genes that are regulated by the top 5% differentially regulated miRNAs after triptolide treatment. The Annals of Thoracic Surgery 2015 100, 1817-1825DOI: (10.1016/j.athoracsur.2015.05.074) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 Triptolide decreases non-small cell lung cancer (NSCLC) migration. Triptolide treatment decreases migration in H460, A549, and H358 cells by using Transwell filters mounted in 4,6-diamidino-2-phenylindole (DAPI)-containing Prolong Gold 27 fields per group. ***p < 0.001, as determined by Student’s t test. The Annals of Thoracic Surgery 2015 100, 1817-1825DOI: (10.1016/j.athoracsur.2015.05.074) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions

Fig 3 Triptolide inhibits non-small cell lung cancer (NSCLC) invasion. Triptolide treatment inhibits invasion of H460, A549, and H358 cells through Matrigel. n = 27 fields per group. ***p < 0.001, as determined by a Student’s t test. The Annals of Thoracic Surgery 2015 100, 1817-1825DOI: (10.1016/j.athoracsur.2015.05.074) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions

Fig 4 Non-small cell lung cancer (NSCLC) cell metastasis is decreased by triptolide treatment. Triptolide treatment (1 mg/kg) three times a week for 9 weeks of nondiabetic severe combined immune deficiency γ (NSG) mice injected with H358 cells decreases metastatic lesions (arrows) compared with control mice (right). n = 9 mice per group. **p < 0.01, as determined by a Student’s t test. [Hematoxylin and eosin; ×5 (top); ×20 (bottom).] The Annals of Thoracic Surgery 2015 100, 1817-1825DOI: (10.1016/j.athoracsur.2015.05.074) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions

Fig 5 (A) Triptolide treatment decreases FAK expression and activity and alters signaling downstream of FAK. H460, A549, and H358 cells treated with 10 nmol/L triptolide on dimethylsulfoxide control for 48 hours were harvested for Western blot analysis of FAK and phosphorylated FAK (Y397). (B) Tyrosine phosphorylation of Src and p130CAS is decreased, the activity of Erk1/2 is increased, and there is no change in paxillin activation after triptolide treatment. (C) MMP14 total protein expression decreased by triptolide treatment. Triptolide slightly alters PYK2 activation. (Con = control; Erk1/2 = extracellular signal-related kinase 1/2; FAK = focal adhesion kinase; GAPDH = glyceraldehyde phosphate; MMP14 = matrix metalloprotease 14; PYK2 = protein tyrosine kinase 2; Trp = triptolide.) The Annals of Thoracic Surgery 2015 100, 1817-1825DOI: (10.1016/j.athoracsur.2015.05.074) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions