Cell viability assay (WST-8, Dojindo), caspase 3/7 activation (Promega), and proliferation assay (ECIS, Applied BioPhysics) were performed. For in vivo studies, forty mice were implanted with subcutaneous HuH7 tumors and divided into four treatment groups (n=10); saline control, sorafenib 10 mg/kg PO daily (S), Minnelide (a pro-drug of triptolide) 0.21 mg/kg 3-Methyladenine purchase IP daily (M), and combination of both (C). Tumor volumes were assessed weekly. Results The combination of triptolide and sorafenib was superior to either drug alone in inducing apoptosis, and decreasing viability (T=45%, S=38%, C = 18% at 48 hours) and
proliferation (T=90%, S=90%, C=75% at 24 hours). After 2 weeks of mice treatment, tumor growth inhibition rates were S = 59%, M = 84%, and C = 95%, while control mice tumor volumes were found increased at 9-fold. When crossed over Venetoclax molecular weight to combination treatment, control mice tumor growth volumes plateaued over the following 2 weeks. (Fig 1) Conclusion The combination of sorafenib and triptolide increased apoptosis and decreased proliferation rate in vitro. Combining sorafenib with Minnelide inhibited tumor growth in vivo with greater efficacy than single agent treatments. In vivo combination treatment allowed for using a lower dose of sorafenib (1 0 mg/kg), which is less than 10% of currently
prescribed dose for HCC patients. Combination treatment could have tremendous translational potential in the management of HCC. Disclosures: Rohit Chugh – Patent Held/Filed: Minneamrita The following people have nothing to disclose: Osama Alsaied, Veena Sangwan, Sulagna Banerjee, Ashok Saluja, Selwyn M. Vickers, Eric Jensen Background: We investigated aberrant microRNA (miRNA) expression in chronic hepatitis B (CHB) related hepatocellular carcinoma (HCC) by comparing miRNA expression of HCC tissue and
non-HCC tissue to reveal which miRNAs are related to the Lonafarnib pathogenesis of HCC development. We also investigated the association between miRNA profiles and tumor characteristics or clinical outcome. Methods: Paired tissue samples (HCC and non-HCC) from resected liver specimens were obtained from 22 patients who underwent curative resection. Microarray was performed to screen miRNAs differentiating HCC and non-HCC tissues in the relative expression. Quantitative real time polymerase chain reaction (PCR) was performed to validate the miRNA microarray data. By using miRBase, target signaling pathways of miRNA were predicted. Results: In microarray, miR-532-3p, miR-106b-5p, miR-224, miR-93-5p were up-regulated in HCC tissues, while miR-139-5p was down-regulated in HCC tissues. miR-7-5p, miR-885-3p were up-regulated in HCC with microvascular invasion compared with HCC without microvascular invasion. miR-224 were up-regulated in recurred HCC than non-recurred HCC after curative resection, while miR-194-3p and miR-192-5p were down-regulated in recurred HCC.