Abstract
Ovarian cancer is the most lethal gynaecologic malignancy. Although there are various subtypes of ovarian cancer, high-grade serous ovarian cancer (HGSOC) accounts for 70% of ovarian cancer deaths. Chemoresistance is the primary reason for the unfavourable prognosis of HGSOC. Kallistatin (KAL), also known as SERPINA4, is part of the serpin family. Kallistatin has been discovered to exert multiple effects on angiogenesis, inflammation and tumour progression. However, the roles and clinical significance of kallistatin in HGSOC remain unclear. Here, we showed that kallistatin was significantly downregulated in HGSOC compared to normal fallopian tube (FT) tissues. Low expression of kallistatin was associated with unfavourable prognosis and platinum resistance in HGSOC. Overexpression of kallistatin significantly inhibited proliferation and metastasis, and enhanced platinum sensitivity and apoptosis in ovarian cancer cells. Collectively, these findings demonstrate that kallistatin serves as a prognostic predictor and provide a potential therapeutic target for HGSOC.
Highlights
Ovarian cancer is the most lethal gynaecologic malignancy and the fifth leading cause of female cancer deaths [1]
We investigated the function of kallistatin in ovarian cancer cell proliferation, migration, invasion, platinum resistance and apoptosis
Expression of kallistatin was significantly downregulated in high-grade serous ovarian cancer (HGSOC) We first analysed the protein level of kallistatin in human HGSOC (n = 8) and normal fallopian tube (FT, n = 7) tissues
Summary
Ovarian cancer is the most lethal gynaecologic malignancy and the fifth leading cause of female cancer deaths [1]. Due to the late occurrence of symptoms, ovarian cancer is usually diagnosed at an advanced stage. Subsequent studies revealed that kallistatin exerted multiple effects on angiogenesis, inflammation. Kallistatin is composed of two functional domains, the heparin-binding site and the active site [12]. Kallistatin inhibits VEGF-induced angiogenesis via the heparin-binding site [13]. The active site is essential for inhibiting tissue kallikrein’s activity [14]. Kallistatin has inhibitory effects in many malignancies such as hepatocellular carcinoma, gastric carcinoma and breast cancer [15,16,17]. The biological functions of kallistatin and its prognostic significance in ovarian cancer remain unclear
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