Oncology reports

Rapamycin inhibits Toll-like receptor 4-induced pro-oncogenic function in head and neck squamous cell carcinoma.

PMID 24737049


Toll-like receptor 4xa0(TLR4) is expressed in head and neck squamous cell carcinomaxa0(HNSCC) cells and is associated with HNSCC cancer progression. Rapamycin has been proven to be efficient for the treatment of HNSCC inxa0vivo, yet the mechanism is not understood and rapamycin demonstrates little effect inxa0vitro. In the present study, the HNSCC cell lines CAL27 and SCC4 were pre-treated with rapamycin then stimulated with a TLR4 ligand lipopolysaccharidexa0(LPS). Cell proliferation, migration, invasion, resistance to TRAIL-induced apoptosis, cytokine production, NF-κB and p65 activation were determined. The results indicated that LPS significantly stimulated HNSCC cell proliferation, cytokine production, migration, invasion and resistance to apoptosis induced by tumor necrosis factorxa0(TNF)-related apoptosis-inducing ligandxa0(TRAIL). Pretreatment with rapamycin significantly attenuated LPS-induced pro-oncogenic effects by inhibiting the activation of NF-κB by LPS. siRNA knockdown of TLR4 in HNSCC cells demonstrated that rapamycin attenuated LPS-induced pro-oncogenic effects via TLR4. Hence, this study suggests rapamycin may be efficient for the treatment of HNSCC by attenuating TLR4-induced pro-oncogenic effects.

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EHU086621 MISSION® esiRNA, esiRNA human TLR4 (esiRNA1)