Anti-EZH2 (aa 1-343) polyclonal antibody

Gastric cancer (GC), a high mortality malignancy, is induced by genetic and epigenetic factors. DNA and histone methylation play critical roles in tumor suppressor genes inactivation.SRBC(serum deprivation response factor-related gene product that binds to the c-kinase), suggested as a tumor suppressor gene, participates in apoptosis, tumor chemoresistance and DNA damage response and is repressed in various cancers. Inspecting the mechanisms underlying SRBC suppression is important for cancer treatments. We investigatedSRBCpromoter DNA methylation status and expression ofSRBCandEZH2histone methyltrasferase in gastric cancer. Also, we surveyedSRBCexpression after 5-azacitidine and UNC1999 treatments of AGS cell line. In current work, we used gastric adenocarcinoma tissues, marginal samples and normal gastric biopsies. DNA methylation was detected by Methylation- Specific PCR and mRNA expression was measured by Real-Time PCR.SRBCpromoter methylation analysis, showed fully and partial methylated versions that were associated with patient's age (p = 0.001).SRBCexpression significantly decreased in GC compare with marginal and normal samples (p-value < 0.001).EZH2showed remarkable up-regulation in GC than controls and demonstrated a strong inverse correlation withSRBCexpression (r = - 0.69). Restoration ofSRBCexpression was observed after 5-azacitidine and UNC1999 applications with a remarkable increase by combinational treatment. We showed thatEZH2plays role inSRBCsilencing in addition to DNA methylation. Our study, suggests that DNA methylation andEZH2are involved inSRBCsilencing and their inhibitors can be considered in cancer treatment investigations to overcome chemoresistance induced bySRBCinactivation.

Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma with a proclivity for systemic dissemination, leading many patients to present with advanced stage disease and fail available treatments. There is a notable lack of targeted therapies for NPC, despite working knowledge of multiple proteins with integral roles in NPC cancer biology. These proteins include EZH2, Snail, eIF4E, and IMPDH, which are all overexpressed in NPC and correlated with poor prognosis. These proteins are known to be modulated by ribavirin, an FDA-approved hepatitis C antiviral that has recently been repurposed as a promising therapeutic in several solid and hematologic malignancies. Here, we investigated the potential of ribavirin as a targeted anticancer agent in five human NPC cell lines. Using cellular growth assays, flow cytometry, BrdU cell proliferation assays, scratch wound assays, and invasion assays, we show in vitro that ribavirin decreases NPC cellular proliferation, migration, and invasion and promotes cell-cycle arrest and cell death. Modulation of EZH2, Snail, eIF4E, IMPDH, mTOR, and cyclin D1 were observed in Western blots and enzymatic activity assays in response to ribavirin treatment. As monotherapy, ribavirin reduced flank tumor growth in multiple NPC xenograft models in vivo. Most importantly, we demonstrate that ribavirin enhanced the effects of radiotherapy, a central component of NPC treatment, both in vitro and in vivo. Our work suggests that NPC responds to ribavirin-mediated EZH2, Snail, eIF4E, IMPDH, and mTOR changes and positions ribavirin for clinical evaluation as a potential addition to our NPC treatment armamentarium.