Gossypol overcomes EGFR-TKIs resistance in non-small cell lung cancer cells by targeting YAP/TAZ and EGFRL858R/T790M - 09/06/19
páginas | 8 |
Iconografías | 14 |
Vídeos | 0 |
Otros | 0 |
Highlights |
• | Gossypol inhibited cell growth and induced apoptosis in H1975 cells harboring GFRL858R/T790 M. |
• | Knockdown of YAP/TAZ sensitized H1975 cells to EGFR-TKIs. |
• | Gossypol decreased the protein level of YAP/TAZ and EGFRL858R/T790 M in H1975 cells. |
• | Gossypol exerted the anti-cancer effects, at least partially, by inhibiting YAP/TAZ activity. |
Abstract |
EGFR tyrosine kinase inhibitors (EGFR-TKIs) improve the progression-free survival of patients with non-small cell lung cancer (NSCLC). However, most patients inevitably developed drug resistance. EGFR T790 M mutation is the major mechanism for resistance to EGFR-TKIs and becomes an obstacle for the treatment of NSCLC patients with EGFR activating mutations. Besides, YAP/TAZ also confers resistance to EGFR-TKIs. Our previous study identified gossypol as a YAP/TAZ inhibitor. In the current study, we found that gossypol inhibited cell growth and induced apoptosis in H1975 cells harboring EGFRL858R/T790M. Also, gossypol treatment sensitized H1975 cells to EGFR-TKIs. Our mechanism studies showed that gossypol decreased the protein level of YAP/TAZ, which was abrogated by the proteasome inhibition. Moreover, over-expression of YAP/TAZ reversed the effects of gossypol on H1975 cells, and YAP/TAZ knockdown sensitized H1975 cells to gossypol treatment. Furthermore, gossypol reduced the protein level of EGFRL858R/T790M and inhibited the downstream ERK1/2 pathway in H1975 cells. Our findings suggested that gossypol might serve a promise drug candidate for overcoming EGFR-TKIs resistance by targeting both YAP/TAZ and EGFRL858R/T790M.
El texto completo de este artículo está disponible en PDF.Abbreviations : EGFR, NSCLC, MEK, EMT, SHP2, ALK, EGFR-TKIs, FDA, YAP, TAZ
Keywords : Gossypol, Non-small cell lung cancer, YAP/TAZ, EGFRL858R/T790M
Esquema
Vol 115
Artículo 108860- juillet 2019 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
El acceso al texto completo de este artículo requiere una suscripción.
Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
La compra de artículos no está disponible en este momento.
¿Ya suscrito a @@106933@@ revista ?