Echinatin inhibits tumor growth and synergizes with chemotherapeutic agents against human bladder cancer cells by activating p38 and suppressing Wnt/β-catenin pathways

作者全名："Wang, Xiaoxuan; Luo, Lijuan; Xu, Jingtao; Lu, Qiuping; Xia, Haichao; Huang, Yanran; Zhang, Lulu; Xie, Liping; Jiwa, Habu; Liang, Shiqiong; Luo, Xiaoji; Luo, Jinyong"

作者地址："[Wang, Xiaoxuan; Luo, Lijuan; Lu, Qiuping; Xia, Haichao; Zhang, Lulu; Xie, Liping; Liang, Shiqiong; Luo, Jinyong] Chongqing Med Univ, Sch Lab Med, Key Lab Diagnost Med Designated, Chinese Minist Educ, Chongqing 400016, Peoples R China; [Xu, Jingtao; Huang, Yanran; Jiwa, Habu; Luo, Xiaoji] Chongqing Med Univ, Dept Orthoped, Affiliated Hosp 1, Chongqing 400042, Peoples R China; [Luo, Jinyong] Chongqing Med Univ, Sch Lab Med, Key Lab Diagnost Med Designated, Chinese Minist Educ, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Luo, JY (通讯作者)，Chongqing Med Univ, Sch Lab Med, Key Lab Diagnost Med Designated, Chinese Minist Educ, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001074901800001

JCR分区：Q1

影响因子：6.9

年份：2024

卷号：11

期号：2

开始页：1050

结束页：1065

文献类型：Article

关键词：Bladder cancer; Combination chemotherapy; Echinatin; p38; Wnt/beta-catenin

摘要："Bladder cancer (BC) is one of the most common malignant tumors in the urinary sys-tem. Due to the poor prognosis and high mortality rate of the disease, it is urgent to develop new drugs with high efficacy and low toxicity to treat BC. Echinatin (Ecn) is a bioactive natural flavonoid oflicorice that has attracted special attention for its promising anti-tumor potential. Herein, we explored the inhibitory effects of Echinatin on BC cells and probed the possible mo-lecular mechanism. We found that Ecnin vitro inhibited the proliferation, migration, and inva-sion, arrested the cell cycle at the G2/M phase, and promoted apoptosis in BC cells. Besides, Ecn had no notable cytotoxicity towards human normal cells. We subsequently confirmed that Ecn restrained xenograft tumor growth and metastasis of BC cells in vivo. Mechanistically, Ecn activated the p38 signaling pathway but inactivated the Wnt/beta-catenin signaling pathway, while over-expression of beta-catenin and the p38 inhibitor both attenuated the inhibitory effects of Ecn on BC cells. Remarkably, Ecn combined with cisplatin (DDP) or gemcitabine (Gem) had synergistic inhibitory effects on BC cells. In summary, our results validate that Ecn inhibits the tumor growth of human BC cells via p38 and Wnt/beta-catenin signaling pathways. Moremeaningfully, our results suggest a potential strategy to enhance DDP-or Gem-induced inhibitory effects on BC 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 (China) [W0086]

基金资助正文：<BOLD>Funding</BOLD> This work was supported by the National Natural Science Foundation of China (No. 81874001) and the Program for Youth Innovation in Future Medicine of Chongqing Medical University (China) (No. W0086) .