Lu Kun, Chao Liu, Wang Jin, Wang Xiangyu, Cai Longjun, Zhang Jianjun, Zhang Shaoqi
Department of Oncology, Suqian Hospital of Nanjing Drum Tower Hospital Group, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, China.
Department of Urology, Suqian Hospital of Nanjing Drum Tower Hospital Group, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, China.
Sci Rep. 2025 Aug 13;15(1):29679. doi: 10.1038/s41598-025-14977-y.
Bladder cancer (BC) is notably prevalent, particularly among men. Emerging evidence highlights that traditional Chinese medicine (TCM) has distinct anticancer properties. This study focuses on recombinant MAP30, a key active constituent of Momordica charantia extract, recognized for its antiviral, immunomodulatory, and antitumor effects. We discovered that MAP30 suppresses BC cell proliferation and induces apoptosis in a dose-responsive manner. It also hinders cell migration, as evidenced by Transwell and wound healing assays. In nude mice, MAP30 injections adjacent to tumors significantly curtail tumor growth. Molecular analyses after MAP30 exposure show elevated SA-β-Gal activity and increased expression of cell cycle inhibitors p21 and p16 in BC cells. Integrating TCGA BC data, MAP30 appears to correct dysregulated gene expression associated with the cell cycle, senescence, apoptosis, and key pathways such as FOXO, TNF, and MAPK. Proteomic analysis identifies CENPA as a central molecule inhibited by MAP30. Correlation studies reveal CENPA's significant association with oncogenic and immune-modulatory gene expression and immune cell infiltration. CENPA knockdown diminishes BC cell growth and motility, while its overexpression in MAP30-treated cells reverses these effects, suggesting CENPA's pivotal role in MAP30's anticancer activity and its potential as a therapeutic target. In conclusion, recombinant MAP30 effectively hampers bladder cancer cell proliferation and migration via CENPA downregulation and induces apoptosis and senescence, offering therapeutic potential against bladder cancer.
膀胱癌(BC)尤为常见,在男性中尤为突出。新出现的证据表明,传统中医(TCM)具有独特的抗癌特性。本研究聚焦于重组MAP30,它是苦瓜提取物的一种关键活性成分,以其抗病毒、免疫调节和抗肿瘤作用而闻名。我们发现MAP30以剂量反应方式抑制膀胱癌细胞增殖并诱导凋亡。Transwell和伤口愈合试验证明,它还能阻碍细胞迁移。在裸鼠中,在肿瘤附近注射MAP30可显著抑制肿瘤生长。MAP30处理后的分子分析显示,膀胱癌细胞中SA-β-Gal活性升高,细胞周期抑制剂p21和p16的表达增加。整合TCGA BC数据后,MAP30似乎能纠正与细胞周期、衰老、凋亡以及FOXO、TNF和MAPK等关键通路相关的基因表达失调。蛋白质组学分析确定CENPA是受MAP30抑制的核心分子。相关性研究揭示CENPA与致癌和免疫调节基因表达以及免疫细胞浸润显著相关。敲低CENPA可减少膀胱癌细胞的生长和运动,而在MAP30处理的细胞中过表达CENPA则可逆转这些作用,这表明CENPA在MAP30的抗癌活性中起关键作用,并且具有作为治疗靶点的潜力。总之,重组MAP30通过下调CENPA有效阻碍膀胱癌细胞的增殖和迁移,并诱导凋亡和衰老,为膀胱癌提供了治疗潜力。