中国医学科学院学报2025，Vol.47Issue(3)：366-374,9.DOI:10.3881/j.issn.1000-503X.16231
组织激肽释放酶7小分子抑制剂对卵巢癌的影响
Effect of the Small Molecule Inhibitor of Kallikrein-Related Peptidase 7 Against Ovarian Cancer
摘要
Abstract
Objective To investigate the effect of the small molecule inhibitor C42 of kallikrein-related peptidase 7(KLK7)on ovarian cancer with elevated expression of KLK7 and evaluate the feasibility of C42 as a new therapeutic strategy for ovarian cancer.Methods The CCK-8 assay,flow cytometry,cell scratch assay,Transwell assay,and Western blotting were employed to assess the effects of C42 on the proliferation,migration,and invasion of the ovarian cancer cell line SKOV3,which was characterized by high KLK7 expression.Addi-tionally,a subcutaneous xenograft model of ovarian cancer was established with SKOV3 cells in nude mice to evaluate the effects of C42 on the tumor growth and metastasis.The expression levels of proteins associated with tumor metastasis and invasion in the tumor tissue were examined by immunohistochemical techniques.Results The cellular experiment showed that C42 suppressed the proliferation,migration,and invasion(all P＜0.001)of SKOV3 cells,compared with the control group.The animal experiment showed that compared with the control group,the 10.2 mg/kg C42 group exhibited a decreased tumor weight(P=0.009)and attenuated liver metasta-ses.Immunohistochemical staining revealed that the 10.2 mg/kg C42 group demonstrated down-regulated expression of the tumor proliferation marker Ki-67(P=0.002)and the tumor metastasis and invasion-associated proteins such as matrix metalloproteinase-9(P=0.027)and Vimentin(P=0.039).Conclusion The small molecule inhibitor C42 of KLK7 effectively suppresses the proliferation,migration,and invasion of ovarian cancer SKOV3 cells.关键词
卵巢癌/组织激肽释放酶7/SKOV3细胞/靶向治疗Key words
ovarian cancer/kallikrein-related peptidase 7/SKOV3 cell/targeted therapy分类
医药卫生引用本文复制引用
时鸿娟,刘伟,胡丽玲,谭潇..组织激肽释放酶7小分子抑制剂对卵巢癌的影响[J].中国医学科学院学报,2025,47(3):366-374,9.基金项目
三峡大学肿瘤微环境与免疫治疗湖北省重点实验室开放基金(2023KZL02、2022KZL2-06)、三峡大学自然科学类委托技术开发项目基金(SDHZ2021245、SDHZ20230118)和宜昌市医疗卫生科研基金(A21-2-004) （2023KZL02、2022KZL2-06）
