Ganoderma immunomodulatory protein and chidamide down-regulate integrin-related signaling pathway result in migration inhibition and apoptosis induction.
Phytomedicine
; 51: 39-47, 2018 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-30466626
ABSTRACT
BACKGROUND:
In terms of melanoma, recent advances have been made in target therapies and immune checkpoint inhibitors, but durable remission is rare. Ganoderma immunomodulatory proteins (GMI) induce a cytotoxic effect in cancer cells via autophagy. However, the role of GMI in melanoma is not clear.PURPOSE:
The aims of this study are to investigate the inhibiting effects of GMI combined with chidamide on survival and metastases of melanoma cells via integrin-related signaling pathway and to propose strategies for combining GMI and chidamide using animal model.METHODS:
Cell viability was measured by cell CCK-8. The activities of apoptosis- and migration-related proteins were detected on Western blot. Flow cytometry was used to analyze cell cycle distribution and sub-G1 fraction in treated melanoma cells. To evaluate the activity of combination GMI and chidamide treatment, an in vivo anti-tumor metastasis study was performed.RESULTS:
GMI combined with chidamide additively induced apoptosis. GMI inhibited the expressions of Integrin α5, αV, ß1, and ß3. The level of p-FAK was inhibited by GMI. Combination treatment of GMI and chidamide decreased survivin and increased cleaved caspase-7 and LC3 II/I. Integrin-αV overexpression activated p-FAK pathways in A375.S2 cells. GMI significantly inhibited cell growth and migration of A375.S2 cells on wound healing assay. In vivo, GMI combined with chidamide suppressed distal tumor metastasis.CONCLUSION:
GMI inhibits the migration and growth of melanoma cells via integrin-related signaling pathway. GMI and chidamide induces apoptosis. In vivo, GMI and chidamide additively reduce distant metastases. GMI and chidamide are potential immunotherapeutic adjuvant for metastatic melanoma.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Benzamidas
/
Melanoma Experimental
/
Transducción de Señal
/
Apoptosis
/
Ganoderma
/
Aminopiridinas
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Phytomedicine
Asunto de la revista:
TERAPIAS COMPLEMENTARES
Año:
2018
Tipo del documento:
Article
País de afiliación:
Taiwán