Norethisterone/Ethinyl estradiol

Objective To investigate the role of nuclear receptor-binding SET domain protein 3 (NSD3) in lipopolysaccharide (LPS)-triggered tumor necrosis factor α (TNF-α) production in macrophages and the underlying epigenetic mechanism. Methods The experiment used murine peritoneal macrophages and RAW264.7 cells as cell models. The mRNA and protein level of NSD3 were detected by real-time quantitative PCR and Western blot analysis in mouse peritoneal macrophages stimulated with LPS (100 ng/mL). ELISA was used to detect the production of TNF-α in NSD3-overexpressing RAW264.7 cells or NSD3-silencing peritoneal macrophages. Western blot analysis was performed to test the activation of LPS-triggered NF-κBp65 in NSD3-silencing macrophages. Luciferase assay was used to assess NF-κBp65-mediated transcriptional activation of TNF-α gene. ChIP assay was used to detect the recruitment of H3K36 methylation to TNF-α gene promoter. Results LPS inhibited the expression of NSD3 in the macrophages. Over-expression of NSD3 suppressed LPS-triggered TNF-α production, and silencing NSD3 promoted LPS-triggered TNF-α production. However, NSD3 had no effect on the activation of LPS-triggered NF-κBp65. NSD3 enhanced NF-κBp65-mediated transcriptional activation of TNF-α gene. NSD3 enhanced the dimethylation of H3K36 of TNF-α gene promoter. Conclusion NSD3 can promote the dimethylation of H3K36 of TNF-α gene promoter and suppress TNF-α transcription and production.

Antiangiogenic therapy is vital in nasopharyngeal carcinoma (NPC) treatment. NPC01 has already been successfully used in treating patients with NPC in clinical practice and exerted an excellent antiangiogenetic effect. However, the potential molecular mechanism underlying the antitumor effect of NPC01 has not been well explored. The present study demonstrated that NPC01 could significantly inhibit cell proliferation and induce cell apoptosis in a dose‐dependent manner in human NPC cell lines. Furthermore, NPC01 exerted antiproliferative and antiangiogenic effects in NPC xenograft mice. Moreover, the study showed that NPC01 could significantly decrease the expression of angiogenesis‐associated factors including hypoxia‐inducible factor‐1α and vascular endothelial growth factor. Additionally, the decreased expression of these angiogenesis‐associated factors could be due to the inhibition of the phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway (PI3K/Akt/mTOR). In conclusion, the results proposed that NPC01 could exert its antitumor effect by suppressing the PI3K/Akt/mTOR signaling pathway. Further studies are warranted to elucidate the molecular mechanism.