Cheng Xiongtao, Sun Jianguo, Chen Shouhong, Wang Nan, Tang Weijing, Xia Zijian, Shu Yuhong, Gao Shouhong, Wang Zhipeng, Wang Xinxia, Shao Rongzi, Cao Jianxiong
Graduate School, Hunan University of Chinese Medicine, Changsha, Hunan, China.
Department of Oncology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.
Front Pharmacol. 2025 Jan 15;15:1517708. doi: 10.3389/fphar.2024.1517708. eCollection 2024.
TRIB3 has been reported to mediate breast cancer (BC) proliferation and metastasis by interacting with AKT1, and blocking the interaction between TRIB3 and AKT1 can inhibit the progression of BC. Besides, inhibiting TRIB3 to turn "cold tumor" hot has also been proved to be an effective therapeutic strategy for BC. Thus, this study aim to find drugs that can bind to TRIB3 to inhibit BC progression, and further elucidate its mechanism.
The possible inhibitors of TRIB3 were screened by high-throughput molecular docking, CETSA, and CO-IP assay. Then, the effect of TRIB3 inhibitor anti BC was assessed by CCK-8 assay, flow cytometry, plate colony formation assay, and transwell assay; and the RNA-seq was empolyed to study the potential mechanism of Parishin B (PB) anti-BC. Finally, the effect of TRIB3 inhibitor on BC lung metastasis was evaluated.
PB was screened as a possible inhibitor of TRIB3, and CETSA and CO-IP assay indicated that PB could target TRIB3 and block TRIB3-AKT1 interaction. In addition, PB exhibited good anti-BC activity without drug toxicity in normal breast cells by experiments , and RNA-seq analysis suggested PB could inhibit the proliferation and invasion of BC cells related with cell cycle. It was also proved that PB could inhibit BC lung metastasis .
The study demonstrated PB can bind to TRIB3 to inhibit BC proliferation and lung metastasis by blocking TRIB3-AKT1 interaction and regulating cell cycle, providing a therapeutic agent for the treatment of BC.
据报道，TRIB3可通过与AKT1相互作用介导乳腺癌（BC）的增殖和转移，阻断TRIB3与AKT1之间的相互作用可抑制BC的进展。此外，抑制TRIB3将“冷肿瘤”转变为“热肿瘤”也已被证明是BC的一种有效治疗策略。因此，本研究旨在寻找能够与TRIB3结合以抑制BC进展的药物，并进一步阐明其机制。
通过高通量分子对接、CETSA和CO-IP实验筛选TRIB3的潜在抑制剂。然后，通过CCK-8实验、流式细胞术、平板克隆形成实验和Transwell实验评估TRIB3抑制剂抗BC的效果；并采用RNA测序研究帕里辛B（PB）抗BC的潜在机制。最后，评估TRIB3抑制剂对BC肺转移的影响。
PB被筛选为TRIB3的一种潜在抑制剂，CETSA和CO-IP实验表明PB可靶向TRIB3并阻断TRIB3-AKT1相互作用。此外，实验表明PB在正常乳腺细胞中表现出良好的抗BC活性且无药物毒性，RNA测序分析表明PB可抑制与细胞周期相关的BC细胞的增殖和侵袭。还证明了PB可抑制BC肺转移。
该研究表明PB可通过阻断TRIB3-AKT1相互作用并调节细胞周期来结合TRIB3以抑制BC增殖和肺转移，为BC的治疗提供了一种治疗药物。
