Title:Pharmacological Mechanisms of Kirenol against Ovarian Carcinoma:
A Network Pharmacology and Experimental Validation Study In Vitro
Volume: 28
Issue: 5
Author(s): Xiaoling Mao, Hong Zhu*, Jun Gao, Shixin Lin, Yin Bao, Mingyue Zhang and Huan Yang
Affiliation:
- Department of Gynecologic Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China
Keywords:
Kiren, ovarian carcinoma, PI3K/AKT/CDK4, cell cycle, apoptosis, metastasis.
Abstract:
Background: Ovarian carcinoma is an aggressive gynecological malignancy. Kirenol,
a diterpene compound, has recently gained attention for its potential anticancer properties. However,
its exact anti-tumor mechanism remains largely unexplored.
Objective: In this study, we explored the inhibitory effects of Kirenol on ovarian cancer using
network pharmacology and in vitro experiments and elucidated its underlying mechanisms.
Methods: Through the utilization of molecular docking, we established a network of proteinprotein
interactions (PPI), which unveiled CDK4 as an essential target. Additionally, gene enrichment
and pathway analysis highlighted the significance of the PI3K/AKT pathway. The viability
of ovarian cancer cells and normal ovarian epithelial cells was evaluated using CCK8 assays
to determine the effect of Kirenol. Following in vitro tests, cell colony formation, wound
healing, flow cytometry, and Western blotting were conducted to assess its impact on cell proliferation,
metastasis, apoptosis, and the cell cycle.
Results: Kirenol significantly reduced the viability of ovarian cancer cells (SKOV3 and A2780)
compared to normal ovarian epithelial cells (IOSE-80). Moreover, Kirenol efficiently suppressed
the growth and movement, caused a cell cycle halt, and stimulated programmed cell death in
SKOV3 and A2780 cells. Through molecular analysis, it was observed that Kirenol increased
the expression of Bax while decreasing the expression of MMP2, MMP9, and Bcl-2. It also attenuated
the phosphorylation of PI3K, AKT, and RB and downregulated CDK4 and CCND1 expression.
Notably, co-treatment with the PI3K pathway inhibitor LY294002 enhanced the inhibitory
effect of Kirenol on ovarian cancer cells.
Conclusion: In summary, the combined results of our network pharmacology analysis and in
vitro tests emphasized that Kirenol hinders the growth of ovarian cancer cells, causes cell cycle
arrest, enhances apoptosis, and hampers migration, possibly by regulating the PI3K/AKT/CDK4
signaling pathway.
