"Andrographolide inhibits the growth of human osteosarcoma cells by suppressing Wnt/beta-catenin, PI3K/AKT and NF-Kappa B signaling pathways"

作者全名："Huang, Huakun; Lu, Qiuping; Yuan, Xiaohui; Zhang, Ping; Ye, Caihong; Wei, Mengqi; Yang, Chunmei; Zhang, Lulu; Huang, Yanran; Luo, Xiaoji; Luo, Jinyong"

作者地址："[Huang, Huakun; Lu, Qiuping; Zhang, Ping; Ye, Caihong; Wei, Mengqi; Yang, Chunmei; Zhang, Lulu; Luo, Jinyong] Chongqing Med Univ, Key Lab Clin Lab Diagnost, Minist Educ, Chongqing 400016, Peoples R China; [Huang, Yanran; Luo, Xiaoji] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped, Chongqing 400016, Peoples R China; [Yuan, Xiaohui] Hubei Univ Arts & Sci, Xiangyang Cent Hosp, Affiliated Hosp, Dept Med Lab, Xiangyang 441021, Hubei, Peoples R China"

通信作者："Luo, JY (通讯作者)，Chongqing Med Univ, Key Lab Clin Lab Diagnost, Minist Educ, Chongqing 400016, Peoples R China."

来源：CHEMICO-BIOLOGICAL INTERACTIONS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000841136700002

JCR分区：Q1

影响因子：5.1

年份：2022

卷号：365

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Andrographolide; Osteosarcoma; Wnt; ?-catenin; PI3K; AKT; NF-?B

摘要："Osteosarcoma (OS) is an aggressive malignant skeletal tumor characterized by an extremely poor prognosis and a high tendency to recur. The frequently used anti-OS chemotherapy regents are often limited by drug resistance and severe adverse events. It is urgent to develop more effective, tolerable and safe drugs for the treatment of OS. Andrographolide (AG), a diterpenoid lactone isolated from Andrographis paniculata, has been proved to possess anti-tumor activity against several human cancer types. In this current study, we evaluated the inhibitory effect of AG on human OS cells and probed the possible mechanism. We found that AG inhibited the proliferation of human OS cells and blocked cell cycle at G2/M phase. Furthermore, AG impeded the migration and invasion, while promoted the apoptosis of human OS cells. Moreover, we found that AG inhibited OS growth and lung metastasis in orthotopic transplantation model. Mechanistically, we demonstrated that AG suppressed the ac-tivity of Wnt/beta-catenin, PI3K/AKT and NF-kappa B signaling pathways. Notably, we validated that AG synergized with the inhibitors of Wnt/beta-catenin, PI3K/AKT and NF-kappa B to suppress the proliferation, migration and invasion of human OS cells. Collectively, our study conclusively demonstrates that AG inhibits the growth of human OS cells, thus, may be a promising candidate for the treatment of OS."

基金机构：National Natural Science Foundation of China [81874001]; Natural Science Foundation Project of Chongqing Science and Technology Commission [cstc2017jcyjAX0196]

基金资助正文：The present research was supported by the National Natural Science Foundation of China (81874001) and the Natural Science Foundation Project of Chongqing Science and Technology Commission (no. cstc2017jcyjAX0196) .