Liensinine Inhibits Osteosarcoma Growth by ROS-Mediated Suppression of the JAK2/STAT3 Signaling Pathway

被引:22
作者
Jia, Fei [1 ,2 ,3 ]
Liu, Yu [1 ,2 ,3 ]
Dou, Xinyu [1 ,2 ,3 ]
Du, Chuanchao [1 ,2 ,3 ]
Mao, Tianli [1 ,2 ,3 ]
Liu, Xiaoguang [1 ,2 ,3 ]
机构
[1] Peking Univ Third Hosp, Dept Orthoped, North Garden St 49, Beijing 100191, Peoples R China
[2] Beijing Key Lab Spinal Dis, Beijing 100191, Peoples R China
[3] Engn Res Ctr Bone & Joint Precis Med, Beijing 100191, Peoples R China
基金
中国国家自然科学基金;
关键词
APOPTOSIS; CANCER; CELLS; PROLIFERATION; ACTIVATION; AUTOPHAGY; PROMOTES; CURCUMIN;
D O I
10.1155/2022/8245614
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Osteosarcoma (OS) is the most common malignancy of bone. Liensinine exerts antitumor effects on cancers of the colon, breast, and gallbladder. However, its antitumor activity in OS remains unclear. This study is aimed at investigating the efficacy of liensinine against OS and the underlying mechanism of action. Cell proliferation, apoptosis, and cycle arrest in OS were detected using the Cell Counting Kit-8 (CCK-8), colony formation, and flow cytometry assays, respectively. The production of reactive oxygen species (ROS), glutathione (GSH) and glutathione disulfide (GSSG) concentrations, and mitochondrial membrane potential (MMP) of OS cells were measured by flow cytometry, colorimetry, and JC-1 staining. The expressions of factors related to apoptosis, cell cycle, and activation of the JAK2/STAT3 pathway were determined by Western blotting. To examine the potential role of ROS, an antioxidant (N-acetyl cysteine, NAC) was used in combination with liensinine. In vivo, we generated a xenograft mouse model to assess its antitumor efficacy. Tissue level expressions of factors related to apoptosis and activation of the JAK2/STAT3 pathway were assessed by immunohistochemistry or Western blotting. Liensinine inhibited the proliferation and induced G0/G1 phase arrest and apoptosis of OS cells in a dose-dependent manner. Additionally, liensinine promoted intracellular ROS production, enhanced the GSSG/GSH ratio, and induced MMP loss and ROS-mediated suppression of the JAK2/STAT3 pathway. NAC significantly attenuated the liensinine-induced antitumor activities and activated the JAK2/STAT3 pathway. In vivo, liensinine effectively inhibited the OS growth and promoted apoptosis; however, it had no negative effect on the internal organs. In conclusion, liensinine-induced ROS production could suppress the activation of the JAK2/STAT3 pathway and inhibit the OS growth both in vivo and in vitro. Our findings provided a new rationale for subsequent academic and clinical research on OS treatment.
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页数:21
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