Shan Shuhua, Niu Jinping, Yin Ruopeng, Shi Jiangying, Zhang Lizhen, Wu Caihong, Li Hanqing, Li Zhuoyu
Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
School of Life Science, Shanxi University, Taiyuan 030006, China.
Acta Pharm Sin B. 2022 Mar;12(3):1254-1270. doi: 10.1016/j.apsb.2021.10.004. Epub 2021 Oct 15.
Molecular targeted therapy has become an emerging promising strategy in cancer treatment, and screening the agents targeting at cancer cell specific targets is very desirable for cancer treatment. Our previous study firstly found that a secretory peroxidase of class III derived from foxtail millet bran (FMBP) exhibited excellent targeting anti-colorectal cancer (CRC) activity and , whereas its underlying target remains unclear. The highlight of present study focuses on the finding that cell surface glucose-regulated protein 78 (csGRP78) abnormally located on CRC is positively correlated with the anti-CRC effects of FMBP, indicating it serves as a potential target of FMBP against CRC. Further, we demonstrated that the combination of FMBP with the nucleotide binding domain (NBD) of csGRP78 interfered with the downstream activation of signal transducer and activator of transcription 3 (STAT3) in CRC cells, thus promoting the intracellular accumulation of reactive oxygen species (ROS) and cell grown inhibition. These phenomena were further confirmed in nude mice tumor model. Collectively, our study highlights csGRP78 acts as an underlying target of FMBP against CRC, uncovering the clinical potential of FMBP as a targeted agent for CRC in the future.
分子靶向治疗已成为癌症治疗中一种新兴的、有前景的策略，筛选针对癌细胞特异性靶点的药物对癌症治疗非常重要。我们之前的研究首次发现，来源于谷子麸皮的III类分泌型过氧化物酶（FMBP）具有出色的靶向抗结直肠癌（CRC）活性，但其潜在靶点尚不清楚。本研究的亮点在于发现，CRC细胞表面异常定位的细胞表面葡萄糖调节蛋白78（csGRP78）与FMBP的抗CRC作用呈正相关，表明它是FMBP抗CRC的潜在靶点。此外，我们证明FMBP与csGRP78的核苷酸结合结构域（NBD）结合会干扰CRC细胞中信号转导和转录激活因子3（STAT3）的下游激活，从而促进细胞内活性氧（ROS）的积累并抑制细胞生长。这些现象在裸鼠肿瘤模型中得到了进一步证实。总的来说，我们的研究突出了csGRP78作为FMBP抗CRC的潜在靶点，揭示了FMBP未来作为CRC靶向药物的临床潜力。
