Details

Autor(en) / Beteiligte

• Lu, Chun-Te
• Leong, Pui-Ying
• Hou, Ting-Yi
• Huang, Sheng-Jia
• Hsiao, Yu-Ping
• Ko, Jiunn-Liang

Titel

Ganoderma immunomodulatory protein and chidamide down-regulate integrin-related signaling pathway result in migration inhibition and apoptosis induction

Ist Teil von

• Phytomedicine (Stuttgart), 2018-12, Vol.51, p.39-47

Ort / Verlag

Germany: Elsevier GmbH

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. GMI combined with chidamide additively induced apoptosis. GMI inhibited the expressions of Integrin α5, αV, β1, and β3. 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. 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. [Display omitted]