YYB-101，一种人源化抗肝细胞生长因子单克隆抗体，抑制卵巢癌细胞迁移和增殖。
YYB-101, a Humanized Antihepatocyte Growth Factor Monoclonal Antibody, Inhibits Ovarian Cancer Cell Motility and Proliferation.
机构信息
Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, Republic of Korea.
Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, Republic of Korea
出版信息
Anticancer Res. 2021 Feb;41(2):671-678. doi: 10.21873/anticanres.14818.
BACKGROUND/AIM: Hepatocyte growth factor (HGF) acts as a key regulator in promoting ovarian cancer metastasis. Previously, we observed that YYB-101, a humanized anti-HGF antibody, effectively inhibits ovarian cancer cell migration, invasion, and progression. Here, we evaluated the signaling mechanisms affected by YYB-101 that are important in ovarian cancer cell progression.
MATERIALS AND METHODS
Using cell migration, invasion and proliferation assays, we evaluated the effects of YYB-101 on A2780/luc and SKOV3 cells. The effects of YYB-101 on signaling molecules were determined by immunocytochemistry and immunoblot analysis.
RESULTS
YYB-101 inhibited HGF-induced ovarian cancer cell motility by down-regulating paxillin phosphorylation and actin-cytoskeleton rearrangement. Also, YYB-101 inhibited ovarian cancer cell proliferation by reducing c-MET phosphorylation and activating apoptosis in vitro and in vivo. These effects were significantly enhanced by combining YYB-101 treatment with paclitaxel, a standard chemotherapy drug.
CONCLUSION
YYB-101 can be examined as a new therapeutic agent for the treatment of patients with ovarian cancer.
背景/目的：肝细胞生长因子（HGF）作为一种关键调节因子，促进卵巢癌转移。此前，我们观察到，一种人源化抗 HGF 抗体 YYB-101，能有效抑制卵巢癌细胞迁移、侵袭和进展。在此，我们评估了 YYB-101 影响卵巢癌细胞进展的重要信号通路机制。
材料与方法
采用细胞迁移、侵袭和增殖实验，评估 YYB-101 对 A2780/luc 和 SKOV3 细胞的影响。通过免疫细胞化学和免疫印迹分析，确定 YYB-101 对信号分子的影响。
结果
YYB-101 通过下调整联蛋白相关蛋白磷酸化和肌动蛋白细胞骨架重排，抑制 HGF 诱导的卵巢癌细胞迁移。此外，YYB-101 通过减少 c-MET 磷酸化和体外及体内激活细胞凋亡，抑制卵巢癌细胞增殖。YYB-101 联合紫杉醇（一种标准化疗药物）治疗，这些作用显著增强。
结论
YYB-101 可作为一种新的治疗卵巢癌患者的治疗药物进行研究。
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