Park Hyun Jin, Choi Garam, Ha Seongmin, Kim Yesl, Choi Min-Jin, Kim Minsup, Islam Md Kamrul, Chang Yongmin, Kwon Tae-Jun, Kim Dongkyu, Jang Eunbee, Kim Tae Hwan, Chang Sha Joung, Kim Yeoun-Hee
R&D Center, Etnova Therapeutics Corp., 124, Sagimakgol-ro, Jungwon-gu, Seongnam-si 13207, Korea.
Institute of Biomedical Engineering Research, Kyungpook National University, 680, Gukchaebosang-ro, Jung-gu, Daegu 41944, Korea.
Cancers (Basel). 2022 Apr 14;14(8):1994. doi: 10.3390/cancers14081994.
Hepatocellular carcinomas (HCCs) are aggressive tumors with a poor prognosis. Approved first-line treatments include sorafenib, lenvatinib, and a combination of atezolizumab and bevacizumab; however, they do not cure HCC. We investigated MBP-11901 as a drug candidate for HCC. Cell proliferation and cytotoxicity were evaluated using normal and cancer human liver cell lines, while Western blotting and flow cytometry evaluated apoptosis. The anticancer effect of MBP-11901 was verified in vitro through migration, invasion, colony formation, and JC-1 MMP assays. In mouse models, the tumor volume, tumor weight, and bodyweight were measured, and cancer cell proliferation and apoptosis were analyzed. The toxicity of MBP-11901 was investigated through GOT/GPT and histological analyses in the liver and kidney. The signaling mechanism of MBP-11901 was investigated through kinase assays, phosphorylation analysis, and in silico docking simulations. Results. MBP-11901 was effective against various human HCC cell lines, leading to the disappearance of most tumors when administered orally in animal models. This effect was dose-dependent, with no differences in efficacy according to administration intervals. MBP-11901 induced anticancer effects by targeting the signaling mechanisms of FLT3, VEGFR2, c-KIT, and PDGFRβ. MBP-11901 is suggested as a novel therapeutic agent for the treatment of advanced or unresectable liver cancer.
肝细胞癌（HCC）是一种侵袭性肿瘤，预后较差。已获批的一线治疗方法包括索拉非尼、仑伐替尼以及阿替利珠单抗和贝伐单抗联合使用；然而，这些方法并不能治愈HCC。我们研究了MBP - 11901作为HCC的候选药物。使用正常和癌性人肝细胞系评估细胞增殖和细胞毒性，同时通过蛋白质免疫印迹法和流式细胞术评估细胞凋亡。通过迁移、侵袭、集落形成和JC - 1线粒体膜电位检测在体外验证了MBP - 11901的抗癌作用。在小鼠模型中，测量肿瘤体积、肿瘤重量和体重，并分析癌细胞增殖和凋亡情况。通过肝脏和肾脏的谷草转氨酶/谷丙转氨酶检测和组织学分析研究了MBP - 11901的毒性。通过激酶检测、磷酸化分析和计算机对接模拟研究了MBP - 11901的信号传导机制。结果。MBP - 11901对多种人HCC细胞系有效，在动物模型中口服给药时可使大多数肿瘤消失。这种效果具有剂量依赖性，给药间隔对疗效无差异。MBP - 11901通过靶向FLT3、VEGFR2、c - KIT和PDGFRβ的信号传导机制诱导抗癌作用。MBP - 11901被认为是治疗晚期或不可切除肝癌的新型治疗药物。
