scholarly journals The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (26) ◽  
pp. 39582-39594 ◽  
Author(s):  
Anuj Suri ◽  
Xiugui Sheng ◽  
Kevin M. Schuler ◽  
Yan Zhong ◽  
Xiaoyun Han ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mouse Model ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Genetically Engineered ◽  
Ovarian Cancer Cells ◽  
Serous Ovarian Cancer ◽  
Genetically Engineered Mouse Model

scholarly journals Anti-Tumor and Anti-Invasive Effects of ONC201 on Ovarian Cancer Cells and a Transgenic Mouse Model of Serous Ovarian Cancer

2021 ◽  
Author(s):  
Yali Fan ◽  
Jiandong Wang ◽  
Ziwei Fang ◽  
Stuart R Pierce ◽  
Lindsay West ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mouse Model ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cellular Stress ◽  
Ovarian Cancer Cells ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Mesenchymal Transition

Abstract Background: ONC201 is a promising first-in-class small molecule that has been reported to have anti-neoplastic activity in various types of cancer through activation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as well as activation of mitochondrial caseinolytic protease P (ClpP).Methods: Our objective was to evaluate the effect of the ONC201 on (1) proliferation, cellular stress, apoptosis and invasion in human serous ovarian cancer (OC) cell lines, and (2) inhibition of tumor growth in a genetically engineered mouse model of high grade serous OC (K18-gT121+/-;p53fl/fl;Brca1fl/fl; KpB) under obese (high fat diet) and lean (low fat diet) conditions. Results: ONC201 significantly suppressed cell proliferation, induced arrest in G1 phase, and increased cellular stress and apoptosis, accompanied by dual inhibition of the AKT/mTOR/S6 and MAPK pathways in OC cells. ONC201 also resulted in inhibition of adhesion and invasion via epithelial–mesenchymal transition and reduction of VEGF expression. Pre-treatment with the anti-oxidant, N-acetylcysteine (NAC), reversed the ONC201-induced oxidative stress response, and prevented ONC201-reduced VEGF and cell invasion by regulating epithelial–mesenchymal transition protein expression. Knockdown of ClpP in ovarian cancer cells reduced ONC201 mediated the anti-tumor activity and cellular stress. Diet-induced obesity accelerated ovarian tumor growth in the KpB mouse model. ONC201 significantly suppressed tumor growth, and decreased serum VEGF production in obese and lean mice, leading to a decrease in tumoral expression of Ki-67, VEGF and phosphorylation of p42/44 and S6 and an increase in ClpP and DRD5, as assessed by immunohistochemistry. Additionally, ONC201 exhibited greater anti-tumor efficacy in obese (75%) as compared to lean (65%) mice. InterpretationConclusions: These results suggest that ONC206 may be a promising therapeutic agent to be explored in future clinical trials in high grade serous OC.

scholarly journals SPR965, a Dual PI3K/mTOR Inhibitor, as a Targeted Therapy in Ovarian Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Arthur-Quan Tran ◽  
Stephanie A. Sullivan ◽  
Leo Li-Ying Chan ◽  
Yajie Yin ◽  
Wenchuan Sun ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Transition Process ◽  
Ovarian Cancer Cells ◽  
Serous Ovarian Cancer ◽  
Mesenchymal Transition

SPR965 is an inhibitor of PI3K and mTOR C1/C2 and has demonstrated anti-tumorigenic activity in a variety of solid tumors. We sought to determine the effects of SPR965 on cell proliferation and tumor growth in human serous ovarian cancer cell lines and a transgenic mouse model of high grade serous ovarian cancer (KpB model) and identify the underlying mechanisms by which SPR965 inhibits cell and tumor growth. SPR965 showed marked anti-proliferative activity by causing cell cycle arrest and inducing cellular stress in ovarian cancer cells. Treatment with SPR965 significantly inhibited tumor growth in KpB mice, accompanied by downregulation of Ki67 and VEGF and upregulation of Bip expression in ovarian tumors. SPR965 also inhibited adhesion and invasion through induction of the epithelial–mesenchymal transition process. As expected, downregulation of phosphorylation of AKT and S6 was observed in SPR965-treated ovarian cancer cells and tumors. Our results suggest that SPR965 has significant anti-tumorigenic effects in serous ovarian cancer in vitro and in vivo. Thus, SPR965 should be evaluated as a promising targeted agent in future clinical trials of ovarian cancer.

scholarly journals Obesity increases tumor aggressiveness in a genetically engineered mouse model of serous ovarian cancer

2014 ◽  
Vol 133 (1) ◽  
pp. 90-97 ◽  
Author(s):  
Liza Makowski ◽  
Chunxiao Zhou ◽  
Yan Zhong ◽  
Pei Fen Kuan ◽  
Cheng Fan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mouse Model ◽  
Genetically Engineered ◽  
Serous Ovarian Cancer ◽  
Tumor Aggressiveness ◽  
Genetically Engineered Mouse Model
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