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

2020 ◽  
Vol 262 ◽  
pp. 113189
Author(s):  
Shuwan Wang ◽  
Jingjing Gao ◽  
Qingyu Li ◽  
Wanjun Ming ◽  
Yanjin Fu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Experimental Verification ◽  
Regulatory Mechanism ◽  
Network Pharmacology

scholarly journals SENP1-mediated deSUMOylation of JAK2 regulates its kinase activity and platinum drug resistance

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Jing Li ◽  
Ruiqin Wu ◽  
Mingo M. H. Yung ◽  
Jing Sun ◽  
Zhuqing Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Kinase Activity ◽  
Regulatory Mechanism ◽  
Platinum Resistance ◽  
Platinum Drug ◽  
Clinical Prognosis ◽  
Platinum Resistant ◽  
Poor Clinical Prognosis ◽  
Stat Pathway

AbstractThe JAK2/STAT pathway is hyperactivated in many cancers, and such hyperactivation is associated with a poor clinical prognosis and drug resistance. The mechanism regulating JAK2 activity is complex. Although translocation of JAK2 between nucleus and cytoplasm is an important regulatory mechanism, how JAK2 translocation is regulated and what is the physiological function of this translocation remain largely unknown. Here, we found that protease SENP1 directly interacts with and deSUMOylates JAK2, and the deSUMOylation of JAK2 leads to its accumulation at cytoplasm, where JAK2 is activated. Significantly, this novel SENP1/JAK2 axis is activated in platinum-resistant ovarian cancer in a manner dependent on a transcription factor RUNX2 and activated RUNX2/SENP1/JAK2 is critical for platinum-resistance in ovarian cancer. To explore the application of anti-SENP1/JAK2 for treatment of platinum-resistant ovarian cancer, we found SENP1 deficiency or treatment by SENP1 inhibitor Momordin Ic significantly overcomes platinum-resistance of ovarian cancer. Thus, this study not only identifies a novel mechanism regulating JAK2 activity, but also provides with a potential approach to treat platinum-resistant ovarian cancer by targeting SENP1/JAK2 pathway.

scholarly journals Network Pharmacology-Based and Clinically Relevant Prediction of the Potential Targets of Chinese Herbs in Ovarian Cancer Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Jing Sun ◽  
Jinfeng Liu ◽  
Dan Liu ◽  
Xiongzhi Wu
Keyword(s):  
Ovarian Cancer ◽  
Regression Analysis ◽  
Protein Expression ◽  
Survival Time ◽  
Signaling Pathway ◽  
Median Survival ◽  
Cox Regression ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Cox Regression Analysis

Reports increasingly suggest that Chinese herbal medicine (CHM) has been used to treat ovarian cancer (OvCa) with a good curative effect; however, the molecular mechanisms underlying CHM are still unclear. In this retrospective study, we explored CHM’s molecular targets for the treatment of OvCa based on clinical data and network pharmacology. We used the Kaplan-Meier method and Cox regression analysis to verify the survival rate of 202 patients with CHM-treated OvCa. The association between CHM and survival time was analyzed by bivariate correlation. A target network of CHM active ingredients against OvCa was established via network pharmacology. Cox regression analysis showed that CHM is an independent favorable prognostic factor. The median survival time was 91 months in the CHM group and 65 months in the non-CHM group. The survival time of FIGO stage III patients in the two groups was 91 months and 52 months, and the median survival period of FIOG stage IV patients was 60 months and 22 months, respectively ( p < 0.001 ). Correlation analysis demonstrated that 12 herbs were closely associated with prognosis, especially in regard to the long-term benefits. Bioinformatics analysis indicated that the anti-OvCa activity of these 12 herbs occurs mainly through the regulation of apoptosis-related protein expression, which promotes OvCa cell apoptosis and inhibits OvCa development. They also regulate the progress of OvCa treatment by promoting or inhibiting protein expression on the p53 signaling pathway and by inhibiting the NF-κB signaling pathway by directly inhibiting NF-κB.

scholarly journals Network Pharmacology-Based Prediction and Verification of the Targets and Mechanism for Panax Notoginseng Saponins against Coronary Heart Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Yan Dong ◽  
Lian Duan ◽  
Heng-wen Chen ◽  
Yong-mei Liu ◽  
Yun Zhang ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Experimental Verification ◽  
Umbilical Vein ◽  
Bioactive Compound ◽  
Panax Notoginseng ◽  
Cardiovascular Death ◽  
Network Pharmacology ◽  
Treatment Target ◽  
Remarkable Effect

Coronary heart disease (CHD) is the worldwide leading cause for cardiovascular death. Panax notoginseng saponin (PNS), which is the main bioactive compound of panax notoginseng, has been generally accepted to exert a remarkable effect on CHD for a long time. However, to reveal the underlying treatment target and corresponding mechanism of PNS against CHD is still a substantial challenge. In this work, the targets and mechanism of PNS against CHD were successfully achieved by pharmacology-based prediction and experimental verification. 36 common targets were screened out through integrating the gene expression profile of CHD and the chemical-protein data of PNS. Then, two key nodes were further selected for verification by experiment after analyzing GO function, KEGG pathway, coexpression, and topology analysis. Results showed that PNS has protected the human umbilical vein endothelial cells from H2O2-induced oxidative stress by inhibiting early cell apoptosis via upregulating VEGFA mRNA expression. Therefore, our research has successfully pointed out one treatment target and apoptotic inhibition caused by PNS with method of integrating bioinformatics prediction and experimental verification, which has partially explained the pharmacological mechanism of PNS against CHD.

scholarly journals Hypoxia-induced up-regulation of miR-27a promotes paclitaxel resistance in ovarian cancer

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Lanlan Feng ◽  
Fangrong Shen ◽  
Jinhua Zhou ◽  
Yan Li ◽  
Rong Jiang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Regulatory Mechanism ◽  
Chemotherapy Resistance ◽  
Paclitaxel Resistance ◽  
In Vivo Experiments ◽  
Hypoxic Environment ◽  
Skov3 Cells

Abstract Ovarian cancer (OC) is a malignant tumor with high mortality in women. Although cancer patients initially respond to paclitaxel chemotherapy following surgery, most patients will relapse after 12–24 months and gradually die from chemotherapy resistance. In OC, cancer cells become resistant to paclitaxel chemotherapy under hypoxic environment. The miR-27a has been identified as an oncogenic molecular in ovarian cancer, prostate cancer, liver cancer etc. In addition, the miR-27a is involved in hypoxia-induced chemoresistance in various cancers. However, the role of miR-27a in hypoxia-induced OC resistance remains unclear. The aim of the present study was to investigate the regulatory mechanism of miR-27a in hypoxia-induced OC resistance. The expression of HIF-1α induced Hypoxia overtly up-regulated. At the same time, hypoxia increased viability of Skov3 cells and decreased cell apoptosis when treated with paclitaxel. The expression of the miR-27a was obviously up-regulated under hypoxia and involved in hypoxia-induced paclitaxel resistance. Follow-up experiments portray that miR-27a improved paclitaxel resistance by restraining the expression of APAF1 in OC. Finally, we further elucidated the important regulatory role of the miR-27a-APAF1 axis in OC through in vivo experiments. According to our knowledge, we first reported the regulation of miR-27a in hypoxia-induced chemoresistance in OC, providing a possible target for chemoresistance treatment of OC.

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