Study on the regulatory mechanism and experimental verification of icariin for the treatment of ovarian cancer based on network pharmacology

Wang, Shuwan; Gao, Jingjing; Li, Qingyu; Ming, Wanjun; Fu, Yanjin; Song, Linliang; Qin, Jiajia

doi:10.1016/j.jep.2020.113189

Cited by 28 publications

(17 citation statements)

References 57 publications

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“…In carboplatin-induced ovarian cancer cells, CYR61 regulates the protein levels of p53 and NF- κ B through the PI3K/AKT/mTOR pathway [ 29 ]. Icariin inhibited the proliferation, migration, and invasion of OC cells SKOV3 in vitro and promoted the OC cell apoptosis by inhibiting the PI3K/AKT signaling pathway [ 23 ]. Therefore, we also hypothesized that FJD's inhibition effect on OC was related to the PI3K/AKT/mTOR/NF- κ B signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…This study may help to provide a novel idea and a theoretical basis for the treatment of OC by TCM. TCM or compounds from TCM have been reported to be of value in the treatment of OC and have achieved good effects [23,24]. Liu et al reported that dihydroartemisinin, a derivative of artemisinin that was separated from the TCM herb Artemisia annua L., could inhibit the proliferation, migration, and invasion of epithelial OC [25].…”

Section: Discussionmentioning

confidence: 99%

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Fuzheng Jiedu Decoction Induces Apoptosis and Enhances Cisplatin Efficacy in Ovarian Cancer Cells In Vitro and In Vivo through Inhibiting the PI3K/AKT/mTOR/NF-κB Signaling Pathway

Yang

et al. 2022

BioMed Research International

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Objectives. This study is aimed at investigating the anticancer activity of Fuzheng Jiedu decoction (FJD) alone or in combination with cisplatin in ovarian cancer (OC) models, as well as its underlying mechanisms of action. Methods. The anticancer activities of FJD, cisplatin, and the combination of the PI3K inhibitor (LY294002, LY) or activator (IGF-1) were evaluated in OC cell lines in vitro and in a SKOV3 xenograft mouse model in vivo. The cell proliferation and invasion ability were measured using MTT, EdU, and transwell assays, respectively. The cell apoptosis was examined by flow cytometry and JC-1 assays. The expression levels of the Bcl-2 family and the PI3K/AKT/mTOR/NF-κB pathway-related proteins were analyzed by Western blot. Results. The in vivo and in vitro studies showed that FJD administration could significantly inhibit cell proliferation and promote cell apoptosis in two OC cell lines SKOV3 and 3AO and partially decreased the tumor volumes and weights. In addition, FJD could significantly downregulate the protein levels of p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, NF-κB, p38, and Bcl-2 and upregulate the Bax, Cyt-C, and cleaved caspase-3 in OC tumor tissues and cells. FJD cotreatment increased the efficacy of cisplatin, including inhibiting OC cell proliferation and invasion, promoting cell apoptosis, and inhibiting the PI3K/AKT/mTOR signaling pathway, while this enhancement was suppressed by IGF-1. Similarly, LY also enhanced the anticancer efficacy of cisplatin. Conclusions. This study indicated that FJD could improve the efficacy of cisplatin by inhibiting the PI3K/AKT/mTOR/NF-κB signaling pathway. It is suggested that FJD may be a valuable adjuvant drug for the treatment of OC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fuzheng Jiedu Decoction Induces Apoptosis and Enhances Cisplatin Efficacy in Ovarian Cancer Cells In Vitro and In Vivo through Inhibiting the PI3K/AKT/mTOR/NF-κB Signaling Pathway

Yang

et al. 2022

BioMed Research International

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“…1A). Then, the 3D SDF format le was uploaded to the SymMap database, and the parameters were set according to the literature [3]. The targets of SKN were imported into Cytoscape 3.7.1 software to establish the C-T network.…”

Section: Prediction Targets Of Skn and Components-targets (C-t) Network Constructionmentioning

confidence: 99%

“…Traditional Chinese medicine (TCM) has been used to effectively treat various diseases for more than 2500 years in China. It has been con rmed that TCM is very advantageous in the clinical application of cancer treatment and is widely accepted as a complementary and alternative therapy with obvious bene cial effects for cancer patients [3]. However, due to the complicated components of TCM, its underlying antitumor mechanisms are not completely understood.…”

Section: Introductionmentioning

confidence: 99%

Network Pharmacology-Based Prediction and Verification of the Mechanism of Shikonin in the Treatment of Colorectal Cancer

Wang

Cui

Shi

et al. 2021

Preprint

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Background: Zicao is the dried root of Lithospermum erythrorhizon Sieb, et Zucc, Arnebia euchroma (Royle) Johnst, or Arnebia guttata Bunge and is commonly used to treat viral infection, inflammation, arthritis, and cancer in traditional Chinese medicine. Shikonin (SKN), a naturally occurring naphthoquinone, is a major active chemical component isolated from Zicao and exhibits anticancer activity according to previous research. However, the underlying mechanism has not been elucidated, so further research is necessary to verify its traditional application. The purpose of the present study was to investigate the antitumor mechanism of SKN in colorectal cancer (CRC) through network pharmacology and experiments.Methods: The SymMap database and GeneCards were adopted to predict the potential targets of SKN and CRC, while cotargets were obtained via a Venn diagram. The cotargets were imported from the String and DAVID websites, the protein-protein interaction (PPI) network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. With regard to the prediction of KEGG by DAVID, the compound-target-pathway network was generated by connecting potential pathways with the corresponding targets. According to the network pharmacological analysis, cytological experiments, real-time PCR (RT-PCR), and Western blot (WB) were used to verify the key signaling pathway.Results: According to the network pharmacological analysis, the most relevant target of SKN to the treatment of colorectal cancer was IL6. GO and KEGG enrichment analyses indicated that various kinases and the PI3K/AKT signaling pathway were the most enriched molecules and pathways. SKN inhibited CRC cell (HT29 and HCT116) proliferation, migration, and invasion and promoted cell apoptosis by targeting IL6 and inhibiting the IL6R/PI3K/AKT signaling pathway.Conclusions: SKN promotes apoptosis and suppresses CRC cell (HT29 and HCT116) activities through the PI3K-Akt signaling pathway. This research not only provides a theoretical and experimental basis for more in-depth studies but also offers an efficient method for the rational utilization of a series of traditional Chinese medicines as anti-CRC drugs.

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“…Excitingly, it has been found that Baohuoside I, a flavonoid compound present in E. koreanum , produces a good inhibitory effect to HCC, during the experiment. Besides, Baohuoside I has been reported to show surprising anticancer effects, including ovarian cancer and lung cancer [13,14,16–18] . Therefore, Baohuoside I isolated from E. koreanum may be a kind of effective anti‐hepatoma treatment scheme.…”

Section: Introductionmentioning

confidence: 99%

Baohuoside I Inhibits the Proliferation of Hepatocellular Carcinoma Cells via Apoptosis Signaling and NF‐kB Pathway

Sun

Pang

Wang

et al. 2021

Chemistry & Biodiversity

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Baohuoside I is a flavonoid isolated from Epimedium koreanum Nakai and has many pharmacological activities. However, its role in liver cancer remains unclear. This study aimed to investigate the inhibitory effect of Baohuoside I on the Human Hepatocellular Carcinoma (HCC) cell lines QGY7703, and underlying mechanisms. QGY7703 cells were used as the model to assess the function of Baohuoside I in vitro. The effects of Baohuoside I on QGY7703 cells’ growth, proliferation, and invasiveness were confirmed by CCK‐8, lactate dehydrogenase release, and invasion assays. Cell apoptosis was analyzed by flow cytometry, and the levels of cleaved Caspase‐3, Bax, and Bcl‐2 were quantified by western blot. Western blot analysis, nuclear translocation of NF‐κB, and Q‐PCR were used to measure the expression of affected molecules. In QGY7703 cells, Baohuoside I induced the expression of molecules related to NF‐κB pathway. The toxicity of Baohuoside I on QGY7703 cells was also confirmed in vivo, in a tumor model. Baohuoside I had a significant toxic effect on QGY7703 cells from a concentration of 10 μM. This compound significantly inhibited the proliferation of QGY7703 cells by inducing apoptosis and downregulating NF‐κB signaling pathway. Thus, Baohuoside I is a novel candidate drug and opens new possibilities of clinical strategies for HCC treatment.

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Study on the regulatory mechanism and experimental verification of icariin for the treatment of ovarian cancer based on network pharmacology

Cited by 28 publications

References 57 publications

Fuzheng Jiedu Decoction Induces Apoptosis and Enhances Cisplatin Efficacy in Ovarian Cancer Cells In Vitro and In Vivo through Inhibiting the PI3K/AKT/mTOR/NF-κB Signaling Pathway

Fuzheng Jiedu Decoction Induces Apoptosis and Enhances Cisplatin Efficacy in Ovarian Cancer Cells In Vitro and In Vivo through Inhibiting the PI3K/AKT/mTOR/NF-κB Signaling Pathway

Network Pharmacology-Based Prediction and Verification of the Mechanism of Shikonin in the Treatment of Colorectal Cancer

Baohuoside I Inhibits the Proliferation of Hepatocellular Carcinoma Cells via Apoptosis Signaling and NF‐kB Pathway

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