Drug Design, Development and Therapy (Aug 2018)
Genetically engineered drug rhCNB induces apoptosis and cell cycle arrest in both gastric cancer cells and hepatoma cells
Abstract
Yanzi Guo,1,* Yonghao Huang,2,* Shuhong Tian,1 Xueli Xie,1 Guilan Xing,1 Jian Fu1 1Key Laboratory of Preclinical Pharmacology and Toxicology of Hainan Province, Hainan Medical College, Haikou 571199, China; 2Key Laboratory of Tropical Diseases and Translational Medicine of the Ministry of Education & Hainan Provincial Key Laboratory of Tropical Medicine, Hainan Medical College, Haikou 571199, China *These authors contributed equally to this work Objectives: Calcineurin B (CNB) is a regulatory subunit of calcineurin, and it has antitumor activity. In this study, we aimed to investigate the effect of recombinant human calcineurin B (rhCNB) on the proliferation of gastric cancer cells and hepatoma cells both in vitro and in vivo.Materials and methods: Cell viability and cell proliferation were detected by MTT and BrdU assay. Flow cytometry, Western blot and immunohistochemistry were performed to determine rhCNB-induced apoptosis and cell cycle arrest. The antitumor activities of rhCNB were observed in mice tumor models.Results: We demonstrated that rhCNB inhibits the proliferation of gastric cancer cells and hepatoma cells both in vitro and in vivo. We showed that the inhibition of cell proliferation by rhCNB is associated with apoptosis and cell cycle arrest in both tumor cell lines. Furthermore, we indicated that rhCNB promotes p53 protein expression, a potent proapoptotic factor. Meanwhile, we also exhibited that rhCNB decreases the expression of both cyclin B1 and CDK1 proteins, two proteins associated with G2/M arrest.Conclusion: Together, these findings suggest that rhCNB markedly inhibits tumor growth and provides guidance for its drug development. Keywords: rhCNB, tumor cells, apoptosis, cell cycle arrest, p53
