Monoclonal antibody AC10364 inhibits cell proliferation in 5-fluorouracil resistant hepatocellular carcinoma via apoptotic pathways

• Main Authors: Wu J, Qu J, Cao H, Jing C, Wang Z, Xu H, Ma R
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-06-01
• Series: OncoTargets and Therapy
• Subjects: monoclonal antibody; inhibitory; apoptosis; genes
• Online Access: https://www.dovepress.com/monoclonal-antibody-ac10364-inhibits-cell-proliferation-in-5-fluoroura-peer-reviewed-article-OTT

Jianzhong Wu,1,* Junwei Qu,1,* Haixia Cao,1 Changwen Jing,1 Zhuo Wang,1 Heng Xu,2 Rong Ma11Research Center for Clinical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu 210000, People’s Republic of China; 2Laboratory of Pharmaceutical Chemistry, Jiangsu Province Institute of Materia Medica, Nanjing Tech University, Nanjing, Jiangsu 211816, People’s Republic of China*These authors contributed equally to this work Background: This study was designed to investigate the antitumor activity of the mAb (AC10364) in vitro and elucidate the related mechanisms of inhibition to cell growth using bel/fu cells treated with AC10364. Methods: The inhibitory effects of AC10364 on the proliferation of Bel/fu cells were examined using a cytotoxicity assay. Apoptosis of Bel/fu cells was detected using FITC annexin V and PI staining following treatment with AC10364 for 24 h. The factors regulating apoptosis were identified by Western blot using lysates of Bel/fu cells treated with AC10364 for 0, 12, 24, or 36 h. Genes associated with tumorigenesis or growth were analyzed by reverse transcription–quantitative polymerase chain reaction using Bel/fu cells treated for 12, 24, or 36 h with AC10364. Results: The early apoptotic ratios of Bel/fu cells treated with AC10364 increased in a dose-dependent manner. The levels of caspases, including cleaved caspase-3, caspase-3 and caspase-9, were significantly high in Bel/fu cells treated with AC10364 (P<0.001). Compared with untreated cells, those exposed to AC10364 had showed significant downregulation of the expression of binding protein gene (G protein subunit α 15, GNA15) and other protein-coding genes, including fms-related tyrosine kinase 1(FLT1), nicotinamide phosphoribosyltransferase (NAMPT), netrin 4 (NTN4), platelet-derived growth factor subunit A (PDGFA), S100 calcium binding protein A11 (S100A11), tubulin β 3 class III (TUBB3), aldo-keto reductase family 1 member C3 (AKR1C3), endothelial PAS domain protein 1 (EPAS1), and interferon α-inducible protein 27 (IFI27) (P<0.001). Two other genes, AXL receptor tyrosine kinase (AXL) and carboxypeptidase A4 (CPA4), were significantly upregulated (P<0.001). Conclusion: AC10364 inhibited cell viability and proliferation through aberrant expression of multiple genes associated with tumorigenesis or growth, which suggests that these genes may be promising therapeutic candidates for cancer therapy.Keywords: monoclonal antibody, inhibitory, apoptosis, genes