scholarly journals NOX4 Signaling Mediates Cancer Development and Therapeutic Resistance through HER3 in Ovarian Cancer Cells

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1647
Author(s):  
Wen-Jing Liu ◽  
Ying-Xue Huang ◽  
Wei Wang ◽  
Ye Zhang ◽  
Bing-Jie Liu ◽  
...  

Development of resistance to therapy in ovarian cancer is a major hinderance for therapeutic efficacy; however, new mechanisms of the resistance remain to be elucidated. NADPH oxidase 4 (NOX4) is responsible for higher NADPH activity to increase reactive oxygen species (ROS) production. In this study, we showed that higher levels of NOX4 were detected in a large portion of human ovarian cancer samples. To understand the molecular mechanism of the NOX4 upregulation, we showed that NOX4 expression was induced by HIF-1α and growth factor such as IGF-1. Furthermore, our results indicated that NOX4 played a pivotal role in chemotherapy and radiotherapy resistance in ovarian cancer cells. We also demonstrated that NOX4 knockdown increased sensitivity of targeted therapy and radiotherapy through decreased expression of HER3 (ERBB3) and NF-κB p65. Taken together, we identified a new HIF-1α/NOX4 signal pathway which induced drug and radiation resistance in ovarian cancer. The finding may provide a new option to overcome the therapeutic resistance of ovarian cancer in the future.

Nanomedicine ◽  
2021 ◽  
Author(s):  
Disha Mittal ◽  
Largee Biswas ◽  
Anita Kamra Verma

Aim: To sensitize cisplatin (Cis)-resistant ovarian cancer cells toward Cis using Cis-loaded nanostructured lipid carriers (CisNLCs). Materials & methods: CisNLCs were synthesized and characterized using dynamic light scattering, Fourier transform IR and x-ray diffraction (XRD). Sensitivity of PA-1 and CaOV3 cells to Cis and its biotoxicity were assessed. Further, expression of the Cis-resistance markers GSTPi and  ATP7B, and apoptotic markers Bax, Bcl2 and Cas9 were quantified by real-time PCR. Results: The size of synthesized CisNLCs was approximately 179.3 ± 2.32 nm and surface charge was -33.9 ± 1.47 mV. IC50 was 210 μg/ml in PA-1 and 500 μg/ml in CaOV3. CisNLCs modulated reactive oxygen species levels in CaOV3 cells. Reduced GSTPi and decreased Cis efflux via ATP7B sequestration caused Cis to accumulate in cytoplasm, thereby augmenting apoptosis in cells. Conclusion: CisNLCs sensitize CaOV3 by redox resetting, indicating their immense therapeutic potential.


2011 ◽  
Vol 25 (8) ◽  
pp. 1712-1720 ◽  
Author(s):  
Aneta Rogalska ◽  
Arkadiusz Gajek ◽  
Marzena Szwed ◽  
Zofia Jóźwiak ◽  
Agnieszka Marczak

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258115
Author(s):  
Demiana H. Hanna ◽  
Gamal R. Saad

Purpose This study aims to prepare folic acid coated tin oxide nanoparticles (FA-SnO2 NPs) for specifically targeting human ovarian cancer cells with minimum side effects against normal cells. Methods The prepared FA-SnO2 NPs were characterized by FT-IR, UV-vis spectroscopy, XRD, SEM and TEM. The inhibition effects of FA-SnO2 NPs against SKOV3 cancer cell were tested by MTT and LDH assay. Apoptosis induction in FA-SnO2 NPs treated SKOV3 cells were investigated using Annexin V/PI, AO/EB and Comet assays and the possible mechanisms of the cytotoxic action were studied by Flow cytometry, qRT-PCR, Immunohistochemistry, and Western blotting analyses. The effects of FA-SnO2 NPs on reactive oxygen species generation in SKOV3 cells were also examined. Additionally, the safety of utilization FA-SnO2 NPs were studied in vivo using Wister rats. Results The obtained FA-SnO2 NPs displayed amorphous spherical morphology with an average diameter of 157 nm and a zeta potential value of -24 mV. Comparing to uncoated SnO2 NPs, FA-SnO2 NPs had a superior inhibition effect towards SKOV3 cell growth that was suggested to be mediated through higher reactive oxygen species generation. It was showed that FA-SnO2 NPs increased significantly the % of apoptotic cells in the sub- G1 and G2/M phases with a higher intensity comet nucleus in SKOV3 treated cells. Furthermore, FA-SnO2 NPs was significantly increased the expression levels of P53, Bax, and cleaved Caspase-3 and accompanied with a significant decrease of Bcl-2 in the treated SKOV3 cells. Conclusion Overall, the results suggested that an increase in cellular FA-SnO2 NPs internalization resulted in a significant induced cytotoxicity in SKOV3 cancer cells in dose-dependent mode through ROS-mediated cell apoptosis that may have occurred through mitochondrial pathway. Additionally, the results confirmed the safety of utilization FA-SnO2 NPs against living systems. So, FA-SnO2 NPs with a specific targeting moiety may be a promising therapeutic candidate for human ovarian cancer.


2020 ◽  
Vol 68 (5) ◽  
pp. 1326-1336 ◽  
Author(s):  
Rongjun Zhang ◽  
Jian Chen ◽  
Lianzhi Mao ◽  
Yajie Guo ◽  
Yuting Hao ◽  
...  

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