Abstract
Yimucao has been used as an herbal medicine to treat gynecological diseases. Common genes of Yimucao active compounds were investigated using network pharmacology. The components and targets of Yimucao were retrieved from the TCMSP database. Cervical cancer targets were collected from GeneCards, TTD, DisGeNET, and KEGG. Cisplatin-related genes were downloaded from GeneWeaver. The protein-protein interaction (PPI) network was created using the STRING database. A drug-bioactive compound-disease-target network was constructed using Cytoscape. GO and KEGG analyses were performed to investigate common targets of quercetin and cisplatin in cervical cancer. We found that quercetin was the highly bioactive compound in Yimucao. The drug-bioactive compound-disease-target network contained 93 nodes and 261 edges. Drug-related key targets were identified, including EGFR, IL6, CASP3, VEGFA, MYC, CCND1, ERBB2, FOS, PPARG, and CASP8. Core targets were primarily related to the response to metal ions, cellular response to xenobiotic stimulus, and transcription factor complex. The KEGG pathway analysis revealed that quercetin and cisplatin may affect cervical cancer through platinum drug resistance and the p53 and HIF-1 pathways. Furthermore, quercetin combined with cisplatin downregulated the expression of EGFR, MYC, CCND1, and ERBB2 proteins and upregulated CASP8 expression in HeLa and SiHa cells. Functionally, quercetin enhanced cisplatin-induced anticancer activity in cervical cancer cells. Our results indicate that quercetin can be used to overcome cisplatin resistance in cervical cancer cells.
Highlights
More than 500,000 women are diagnosed with cervical cancer each year, which causes more than 300,000 deaths worldwide [1]
The predicted results indicated that quercetin and cisplatin interacted with 43 targets related to cervical cancer
The synergistic inhibitory effects of quercetin and cisplatin on cervical cancer cells were observed in our previous study [18]
Summary
More than 500,000 women are diagnosed with cervical cancer each year, which causes more than 300,000 deaths worldwide [1]. The standardized incidence rate of cervical cancer is expected to be 13.1 cases per 100,000 women worldwide [2]. Advanced or recurrent cervical cancer conveys a poor prognosis with a 10–20% 1-year relative survival rate [3]. Predicting Mechanisms of Quercetin and Cisplatin advanced cervical cancer include brachytherapy, external beam radiotherapy, and concurrent chemotherapy based on cisplatin [4]. 40% of locally advanced cervical cancer patients still experience disease recurrence [5]. An economic cost estimate based on cervical cancer demonstrated that per capita expenditures of cervical cancer treatment ranged from US$368 to 11,400 [6]. Traditional Chinese medicine (TCM) has been applied to treat cancer, having the advantage of acting on a variety of cancer-related signaling pathways and molecular targets without severe side effects [7]
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