scholarly journals Ellagic acid inhibited cervical cancer growth via blocking the AKT/mTOR/STAT3 pathway

Author(s):  
Jinyu Xia ◽  
Chunyu Xue ◽  
Jie Yu

IntroductionEllagic acid (EA) is a kind of herb extract. However, the effects and mechanisms of EA in cervical cancer treatment are unclear.Material and methodsOur present work investigated the effects of EA on HeLa cervical cancer cell biological activities and relative mechanisms. Hela cells were divided into 5 groups as the NC group, Low group, Middle group, High group and 5-Fu group. MTT assay and cell apoptosis assay were performed to evaluate cell proliferation and apoptosis. Wound closure assay was used to assess the effect of EA on HeLa cell migration. We also assessed the anti-tumor effect of EA on a cervical tumor bearing BALB/c mouse model. Furthermore, western blotting and immunohistochemistry assay were performed to evaluate the effect of EA on the activation of AKT/mTOR/STAT3 in vitro and in vivo.ResultsThe cell experiments showed that EA had effects to inhibit Hela cell biological activities including cell apoptosis, migration and invasion dose-dependently and AKT, mTOR, and STAT3 phosphorylation expression levels were significantly depressed after EA supplementation in the in vitro study. In the in vivo study, EA significantly depressed tumor growth with cell apoptosis significantly increasing and the AKT/mTOR/STAT3 pathway was significantly down-regulated in tumor tissues.ConclusionsEA had anti-tumor effects on cervical cancer by depressing the AKT/mTOR/STAT3 pathway in in vitro and in vivo study.

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Mariana Segovia-Mendoza ◽  
Rafael Jurado ◽  
Roser Mir ◽  
Luis A Medina ◽  
Heriberto Prado-Garcia ◽  
...  

2020 ◽  
Author(s):  
Xiaofei Jiang ◽  
Mingqing Shi ◽  
Miao Sui ◽  
Yizhen Yuan ◽  
Shuang Zhang ◽  
...  

Abstract Background: Cervical cancer continues to be the leading cause of cancer deaths among women worldwide. Oleanolic acid (OA) is a naturally occurring substance found in the leaves, fruits, and rhizomes of plants that has anti-cancer activity. Methods: We used tumor-bearing mice as the animal model and Hela cell as cell models. Western blot was used for detecting the expression of proteins in ferroptosis related proteins acyl-CoA synthase long-chain family member 4 (ACSL4), ferritin heavy chain (FTH1), transferrin receptor (TfR1) and glutathione peroxidase 4 (GPX4) in vivo and in vitro. MTT and EdU was for the detection of the viability of Hela cells. Results: In vivo experiments showed that OA significantly reduced the size and mass of cervical cancer tumors. In vitro experiments showed that OA significantly reduced the viability and proliferation capacity of Hela cells. In both in vivo and in vitro assays, OA increased the level of oxidative stress and Fe2+ content, and increased the expression of ferroptosis related proteins. We found high expression of ACSL4 in both xenograft models and cervical carcinoma cells. Meanwhile, knockdown of ACSL4 expression using shRNA in cervical cancer cells significantly increased cell viability and proliferation. In addition, decreased ROS levels and GPX4 were detected in ACSL4 knockdown cervical cancer cells, suggesting that ACSL4 inhibition may contribute to the reduction of ferroptosis within Hela cells and thus improve Hela cell survival. Conclusion: Promotion of ACSL4 dependent ferroptosis through OA may be an effective approach to treat cervical cancer.


2019 ◽  
Vol 9 (11) ◽  
pp. 1512-1519
Author(s):  
Caiyan Xu ◽  
Jianjun Zhai ◽  
Yujing Fu

Objection: The purpose of this work was to discuss the effects and relative mechanisms of F11-AS1 in cervical cancer treatment by vitro study. Methods: 20 pairs of cervical carcinoma and adjacent normal tissue were collected and measured pathology and F11-AS1 expression by HE and HIS staining. Measuring F11-AS1 expression in difference cell lines and cell groups by RT-qPCR assay. Transfection F11-AS1 in Hela cells, evaluating hela cell biological including proliferation, apoptosis, invasion and migration by MTT, flow cytometry, transwell and wound healing assay. PTEN, p-PI3K and AKT proteins expression were evaluated by WB assay, and p-PI3K nuclear volume were measured by cellular immunofluorescence assay. Results: F11-AS1 level of cancer tissues were significantly down-regulation with state increasing by ISH assay (P < 0.01, respectively). After transfection with F11-AS1, the Hela cell proliferation rate was significantly down-regulation with apoptosis significantly increasing (P < 0.05); The invasion Hela cell number and wound healing rate were significantly depressed with F11-AS1 transfection (P < 0.05). By WB assay, PTEN protein expression was significantly increasing, and p-PI3K and AKT proteins expression were significantly inhibited (P < 0.05). By cellular immunofluorescence assay, p-PI3K nuclear volume of pcDNA3.1/F11-AS1 group was significantly depressed (P < 0.05). Conclusion: lncRNA F11-AS1 suppressed cervical cancer biological activities by regulation PTEN/p-PI3K/AKT pathway in vitro study.


2019 ◽  
Vol Volume 11 ◽  
pp. 7557-7566 ◽  
Author(s):  
Huijuan Zhang ◽  
Jing Zhang ◽  
Puja S Venkat ◽  
Chenglei Gu ◽  
Yuanguang Meng

Toxicology ◽  
2009 ◽  
Vol 257 (1-2) ◽  
pp. 80-85 ◽  
Author(s):  
Hua-Nan Li ◽  
Fei-Fei Nie ◽  
Wei Liu ◽  
Qin-Sheng Dai ◽  
Na Lu ◽  
...  

2021 ◽  
Vol 22 (16) ◽  
pp. 8693
Author(s):  
Leekyung Kim ◽  
Sun-Ae Park ◽  
Hyemin Park ◽  
Heejung Kim ◽  
Tae-Hwe Heo

Persistent HPV (Human Papillomavirus) infection is the primary cause of cervical cancer. Despite the development of the HPV vaccine to prevent infections, cervical cancer is still a fatal malignant tumor and metastatic disease, and it is often difficult to treat, so a new treatment strategy is needed. The FDA-approved drug Bazedoxifene is a novel inhibitor of protein–protein interactions between IL-6 and GP130. Multiple ligand simultaneous docking and drug repositioning approaches have demonstrated that an IL-6/GP130 inhibitor can act as a selective estrogen modulator. However, the molecular basis for GP130 activation in cervical cancer remains unclear. In this study, we investigated the anticancer properties of Bazedoxifene in HPV-positive cervical cancer cells. In vitro and in vivo experiments showed that Bazedoxifene inhibited cell invasion, migration, colony formation, and tumor growth in cervical cancer cells. We also confirmed that Bazedoxifene inhibits the GP130/STAT3 pathway and suppresses the EMT (Epithelial-mesenchymal transition) sub-signal. Thus, these data not only suggest a molecular mechanism by which the GP130/STAT3 pathway may promote cancer, but also may provide a basis for cervical cancer replacement therapy.


2021 ◽  
Author(s):  
Ziyan Xu ◽  
Liru Huang ◽  
Tiantian Zhang ◽  
Yuwei Liu ◽  
Mei Gong ◽  
...  

Abstract Cervical cancer is one of the most common female cancers worldwide, and it is one of the most lethal malignancies of the female reproductive system. Shikonin, a natural pigment of theophyllin, has a variety of biological activities and has shown significant inhibitory effects on a variety of tumours in vitro and in vivo. However, there are few studies on Shikonin in cervical cancer. In the present study, we found that Shikonin inhibited not only the proliferation but also the migration of cervical cancer cells. Our data showed that Shikonin inhibited the proliferation of HeLa and SiHa cells in a concentration- and time-dependent manner. In cervical cancer cells, Shikonin not only inhibited the phosphorylation of FAK, AKT and GSK3β but also inhibited the phosphorylation of FAK, AKT and GSK3β induced by EGF. Further exploring the mechanism, we found that Shikonin could inhibit the proliferation of cervical cancer cells by regulating the phosphorylation of the FAK/AKT/GSK3β pathway. In addition, Shikonin significantly inhibited cell migration and reduced the expression of proteins such as MTA1, TGFβ1 and VEGF. In conclusion, our study elucidated that Shikonin has an inhibitory effect on the proliferation and migration of cervical cancer cells, which may be mediated by the FAK/AKT/GSK3β signalling pathway. Our results suggest that Shikonin has the potential to become a clinical treatment for cervical cancer.


2019 ◽  
Vol 48 (16) ◽  
pp. 5352-5360 ◽  
Author(s):  
Ting Meng ◽  
Qi-Pin Qin ◽  
Zi-Lu Chen ◽  
Hua-Hong Zou ◽  
Kai Wang ◽  
...  

MClClQ-RuCl induced HeLa cell apoptosis was mediated by the inhibition of telomerase activity and dysfunction of mitochondria. Remarkably, MClClQ-RuCl obviously inhibited HeLa xenograft tumor growth in vivo.


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