SUN Hao,ZHENG Yongquan,XU Mengjin. Target network recognition and compatibility mechanism of Astragalus-Zedoary inducing apoptosis of cervical cancer cells[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2022, 52(8): 603-612.
Abstract：Objective: To identify the target network of Astragalus-Zedoary inducing apoptosis of cervical cancer cells and explore their compatibility mechanism. Methods: First, the cervical cancer disease network was constructed by bioinformatics and the background network was obtained by GO clustering, and the potential key targets were identified by K-means analysis. Then, apoptosis-related target network was identified by k-core decomposition of apoptosis-related sub-networks in the background network. Subsequently, potential key targets in the target network were evaluated by molecular docking and TOPSIS, and potential active ingredients were identified at the same time. Finally, the cell and molecular experiments such as CCK-8 method, TUNEL staining,flow cytometry and Western blot analysis were used to evaluate the ability of Astragalus-Zedoary to induce apoptosis of cervical cancer SiHa cells and to explore the potential compatibility mechanism. Results: The network pharmacology analysis showed that potential active ingredients of 64 Astragalus and 44 Zedoary synergistically regulated the target network composed of 14 potential key targets, while the vast majority of Astragalus (60) and Zedoary (38) ingredients acted on the p53 and β-catenin, respectively. The experimental results showed that the IC50 of Astragalus-Zedoary aqueous extract at 24 h and 48 h were 62.47 mg/mL and 50.37 mg/mL, respectively.Meanwhile, Astragalus-Zedoary aqueous extract could induce G0/G1 phase arrest and early apoptosis in cervical cancer SiHa cells. In addition, Astragalus-Zedoary aqueous extract could increase the expression level of p53 (P<0.05), but the effect on β-catenin is not obvious (P>0.05). Conclusion: Astragalus-Zedoary might synergistically regulate the target network dominated by p53 through its multiple active ingredients, so as to arrest the cell cycle in G0/G1 phase, thereby inducing early apoptosis of cervical cancer cells.
