Hint1 Overexpression Inhibits the Cell Cycle and Induces Cell Apoptosis in Human Osteosarcoma Cells

Dong-Dong Duan,1 Hui Xie,1 Hua-Feng Shi,1 Wen-Wen Huang,1 Fan Ding,1 Jia-Kun Hong,1 Jun-Sheng Fan,1 Shou-Yong Hu,1 Qing-Wei Wang,1 Meng-Qiao Zhou2 1Department of Orthopedic Surgery, The First People’s Hospital of Jingmen, Jingmen, Hubei 448000, People’s Republic of China; 2Department of Cardiology, The First People’s Hospital of Jingmen, Jingmen, Hubei 448000, People’s Republic of ChinaCorrespondence: Meng-Qiao ZhouDepartment of Cardiology, The First People’s Hospital of Jingmen, 67 Xiangshan Avenue, Jingmen, Hubei 448000, People’s Republic of ChinaEmail dddan1120@163.comBackground: New evidence suggests that histidine triad nucleotide-binding protein 1 (Hint1) exerts a tumor suppressor effect in various human tumors, such as colorectal cancer and gastric cancer. However, it has not been reported whether Hint1 is involved in the occurrence and development of osteosarcoma (OS).Materials and Methods: The present study investigated the role of Hint1 in human OS cells by using cell lines, including 143B, U2OS, KHOS-240S, Saos-2 and MG-63. Cell proliferation and apoptosis were detected by flow cytometry.Results: The present result revealed that Hint1 is downregulated in these cell lines. The overexpression of Hint1 by adenovirus transfection in 143B and MG63 cell lines suppressed the proliferation and cell cycle, and increased the cell apoptosis. Mechanically, it was found that Hint1 downregulated the cyclin D1 expression via FOXO1 inhibition. Furthermore, FOXO1 overexpression in the 143B and MG63 cell lines significantly blurred the effects of Hint1 on cellular proliferation and apoptosis.Conclusion: The present study indicates that Hint1 inhibits the development of OS by regulating FoxO1-cyclin D1, suggesting that Hint1 may be a new method for the treatment of OS.Keywords: osteosarcoma, histidine triad nucleotide-binding protein 1, cell cycle, apoptosis, FOXO1