Echinatin inhibits the growth and metastasis of human osteosarcoma cells through Wnt/beta-catenin and p38 signaling pathways

作者全名："Lu, Qiuping; Huang, Huakun; Wang, Xiaoxuan; Luo, Lijuan; Xia, Haichao; Zhang, Lulu; Xu, Jingtao; Huang, Yanran; Luo, Xiaoji; Luo, Jinyong"

作者地址："[Lu, Qiuping; Huang, Huakun; Wang, Xiaoxuan; Luo, Lijuan; Xia, Haichao; Zhang, Lulu; Luo, Jinyong] Chongqing Med Univ, Coll Lab Med, Key Lab Diagnost Med, Chinese Minist Educ, Chongqing 40016, Peoples R China; [Xu, Jingtao; Huang, Yanran; Luo, Xiaoji] Chongqing Med Univ, Dept Orthoped, Affiliated Hosp 1, Chongqing 40016, Peoples R China; [Luo, Jinyong] Chongqing Med Univ, Key Lab Diagnost Med, Chinese Minist Educ, 1 Yixueyuan Rd, Chongqing, Peoples R China"

通信作者："Luo, JY (通讯作者)，Chongqing Med Univ, Key Lab Diagnost Med, Chinese Minist Educ, 1 Yixueyuan Rd, Chongqing, Peoples R China."

来源：PHARMACOLOGICAL RESEARCH

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000976482000001

JCR分区：Q1

影响因子：9.1

年份：2023

卷号：191

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Osteosarcoma; Echinatin; Wnt/beta-catenin; P38; Signaling pathway

摘要："Osteosarcoma (OS) is a highly aggressive malignant bone tumor that mainly occurs in adolescents. At present, chemotherapy is the most commonly used method in clinical practice to treat OS. However, due to drug resistance, toxicity and long-term side effects, chemotherapy can't always provide sufficient benefits for OS patients, especially those with metastasis and recurrence. Natural products have long been an excellent source of antitumor drug development. In the current study, we evaluated the anti-OS activity of Echinatin (Ecn), a natural active component from the roots and rhizomes of licorice, and explored the possible mechanism. We found that Ecn inhibited the proliferation of human OS cells and blocked cell cycle at S phase. In addition, Ecn suppressed the migration and invasion, while induced the apoptosis of human OS cells. However, Ecn had less cytotoxicity against normal cells. Moreover, Ecn inhibited the xenograft tumor growth of OS cells in vivo. Mechanistically, Ecn inactivated Wnt/beta-catenin signaling pathway while activated p38 signaling pathway. beta-catenin overexpression and the p38 inhibitor SB203580 both attenuated the inhibitory effect of Ecn on OS cells. Notably, we demonstrated that Ecn exhibited synergistic inhibitory effect with cisplatin (DDP) on OS cells in vitro and in vivo. Therefore, our results suggest that Ecn may exert anti-OS effects at least partly through regulating Wnt/ beta-catenin and p38 signaling pathways. Most meaningfully, the results obtained suggest a potential strategy to improve the DDP-induced tumor-killing effect on OS cells by combining with Ecn."

基金机构：National Natural Science Foundation of China [81874001]; Program for Youth Innovation in Future Medicine of Chongqing Medical University [W0086]

基金资助正文：The present study was supported by the National Natural Science Foundation of China (Grant No. 81874001) and the Program for Youth Innovation in Future Medicine of Chongqing Medical University (No. W0086) .