Our results suggest that Stat3-targeted therapy is a new therapeutic strategy to overcome the acquired resistance to vemurafenib in the treatment of melanoma.
MSCs carrying Adv-Stat3(-) caused viral amplification, depletion of Stat3 and its downstream proteins, and led to significant apoptosis in breast cancer and melanoma cell lines.
In vivo experiments indicated that topical application of STAT3 siRNA PEI complex delivered by dissolving MNs into skin can effectively suppress the development of melanoma through silencing STAT3 gene, and the inhibition effect is dose-dependent.
Plumbagin and Celecoxib are two agents that were identified to synergistically kill melanoma cells by inhibiting the COX-2 and STAT3 pathways, which are constitutively activated in up to 70% of melanomas.
Furthermore, we demonstrated that melanoma B7-H3 expression was correlated to phosphorylated signal transducer and activator of transcription-3 activity level in melanoma tissues and cell lines.
Changes at genomic, transcriptional and post-translational levels of G-proteins and protein kinases (Ras, B-Raf) and their transcription factor effectors (c-Jun, ATF2, Stat3 and NF-kappaB) affects TNF, Fas and TRAIL receptors, which play important roles in acquiring melanoma's resistance to apoptosis.
Blocking Stat3 signaling in the melanoma cells containing high Stat3 activity results in expression of multiple chemoattractants, leading to increased migration of lymphocytes, NK cells, neutrophils, and macrophages.
STAT3 signaling has been implicated in the pathogenesis of melanoma and constitutive activated STAT3 has been validated can as a target for melanoma therapy.
IFNs and siRNA targeting signal transducer and activator of transcription 3 (STAT3), which is a major immune suppressive transcription factor in melanoma, were delivered simultaneously into the tumor milieu.
In this study, we investigated the clinical role of STAT3 and its natural inhibitor, suppressor of cytokine signaling 3 (SOCS3), in human cutaneous melanoma development and progression.
Thus, the novel modified RNA oligonucleotides targeting STAT3 may serve as a useful tool to study the involvement of STAT3 in melanoma and potentially as an anti-cancer agent for melanoma.
Of the genes identified, seven genes: galectin 3 (Lgals3), melanoma cell adhesion molecule (Mcam), fibronectin 1 (Fn1), signal transducer and activator of transcription 3 (Stat3), microphthalmia-associated transcription factor (Mitf), max interacting protein 1 (Max1), and non-metastatic cells 1, protein (NM23A) expressed in (Nme1) are known to be associated with melanoma, but have not yet been reported as being regulated by hypoxia in human melanoma cells.