Tehran University of Medical Sciences Iranian Journal of Public Health 2251-6085 51 12 2022 12 17 2773 2782 Wenhua Xing The Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia, 10030, China Yanbin Zhao Health Care Center of Ning Bo Customs, Ningbo City, Zhejiang Province, 315012, China Liuwan Lin The Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia, 10030, China Zhenqun Zhao The Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia, 10030, China Mengchen Yang The Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia, 10030, China Na Wang The Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia, 10030, China Shuxia Cui The Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia, 10030, China Rui Bai The Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia, 10030, China Aiqing Zhao Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, 10030, China 2022 06 30 2022 09 02 Background: Osteosarcoma is the most common primary malignant tumor of bone. Abnormal expression of S100A1 protein is closely related to the occurrence and development of malignant tumors. However, S100A1 in osteosarcoma has not been studied. Methods: All osteosarcoma tissues were collected from patients who received surgical therapy at the Affiliated Hospital of Inner Mongolia Medical University, China in 2020. QRT-PCR and western blot assays were used to detect the expression of S100A1 in osteosarcoma tissues and cells. The negative effect of S100A1 on osteosarcoma cell growth was confirmed by vitro and vivo experiments. Results: S100A1 inhibited the growth of osteosarcoma cells in vitro. Overexpression of S100A1 may inhibit the proliferation of osteosarcoma cells by preventing the activation of AKT signaling pathway by western blot assay. Finally, animal experiments confirmed that overexpression of S100A1 could inhibit the proliferation of osteosarcoma cells. Overexpression of S100A1 obtained better survival benefit in mice. Conclusion: Our findings provided a new insight to the treatment of osteosarcoma. It also raised the possibility that S100A1 could be used in targeted therapies for osteosarcoma. https://ijph.tums.ac.ir/index.php/ijph/article/view/29144 https://ijph.tums.ac.ir/index.php/ijph/article/download/29144/7808