Effect of the Small Molecule Inhibitor of Kallikrein-Related Peptidase 7 Against Ovarian CancerA.
10.3881/j.issn.1000-503X.16231
- Author:
Hong-Juan SHI
1
;
Wei LIU
2
;
Li-Ling HU
3
;
Xiao TAN
1
Author Information
1. Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy,College of Basic Medical Sciences,China Three Gorges University,Yichang,Hubei 443002,China.
2. Department of Hepatobiliary and Pancreatic Surgery,The First College of Clinical Medical Science, China Three Gorges University,Yichang,Hubei 443003,China.
3. Center of Drug Clinical Trial,The First College of Clinical Medical Science, China Three Gorges University,Yichang,Hubei 443003,China.
- Publication Type:Journal Article
- Keywords:
SKOV3 cell;
kallikrein-related peptidase 7;
ovarian cancer;
targeted therapy
- MeSH:
Female;
Humans;
Ovarian Neoplasms/drug therapy*;
Kallikreins/antagonists & inhibitors*;
Animals;
Mice, Nude;
Cell Line, Tumor;
Cell Proliferation/drug effects*;
Mice;
Cell Movement/drug effects*;
Xenograft Model Antitumor Assays;
Mice, Inbred BALB C
- From:
Acta Academiae Medicinae Sinicae
2025;47(3):366-374
- CountryChina
- Language:English
-
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.Additionally,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 metastases.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.
