Effects of phosphoinositide 3-kinase inhibitor SHBM1009 on cancer cells proliferation

2018 ◽  
pp. 1-7
Author(s):  
Dujiao Wu ◽  
LiHao Huang ◽  
Qi Shen ◽  
Bijun Zhu
Keyword(s):  
Tumor Progression ◽  
Cancer Cells ◽  
Digestive System ◽  
Cellular Proliferation ◽  
Kinase Inhibitor ◽  
Pi3k Inhibitor ◽  
Therapeutic Effects ◽  
Potential Mechanism ◽  
Phosphoinositide 3 Kinase

Abstract: Phosphoinositide 3-kinase (PI3K) plays an important role in cellular proliferation and tumor progression. The objective of this study is to evaluate the potential mechanism and therapeutic effects of new PI3K inhibitor SHBM1009 on various cancer cells of digestive system on proliferation.  

Effects of phosphoinositide 3-kinase inhibitor SHBM1009 on cancer cells proliferation

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Lingyan Wang ◽  
Li-Hao Huang ◽  
Qi Shen ◽  
Fangming Liu ◽  
Bijun Zhu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cellular Proliferation ◽  
Kinase Inhibitor ◽  
Critical Role ◽  
Cell Number ◽  
Pi3k Inhibitor ◽  
Therapeutic Effects ◽  
Recording Time ◽  
Cell Functions ◽  
Phosphoinositide 3 Kinase

BACKGROUND: Phosphoinositide 3-kinase (PI3K) plays an important role in cellular proliferation  and tumor progression. The objective of this study is to evaluate the potential mechanism and therapeutic effects of new PI3K inhibitor SHBM1009 on various cancer cells of digestive system on proliferation. METHODS: Six human hepatocellular carcinoma cell lines including 97H, 97L, A3, F11, MHCC-1, SMMC7721, one gastric cell line SGC-7901 and three primary testicular cancer TYST,TYST1,TYST2 cells were treated by 100ng/ml epidermal growth factor with or without 1uM NVP-BEZ-235 and SHBM1009  in Cell-IQ system in 24-well plates for 48h and up to 72h. The cell bio-behaviors, especially for cell proliferation of total cell number were measured by a real-time cell monitoring system, Cell-IQ continuous cell culturing platform. Images were captured at 30 min intervals. Cell-IQ system uses machine vision technology for monitoring and recording time-lapse data, and the cell functions and morphological parameters were quantified and analyzed. RESULTS: SHBM1009 could prevent EGF-induced cancer cells proliferation. Different patterns of inhibitory effects of SHBM1009 and NVP-BEZ-235, a dual PI3K/mechanistic target of rapamycin inhibitor, on EGF-induced cancer cells proliferation were observed. CONCLUSIONS: PI3K plays a critical role in the development of cancer progress, including proliferation, differentiation and anti-apoptosis. SHBM1009, a new PI3K inhibitor, could be new therapeutic alternatives for cancer treatment.

scholarly journals The Brain Penetrating and Dual TORC1/TORC2 Inhibitor, RES529, Elicits Anti-Glioma Activity and Enhances the Therapeutic Effects of Anti-Angiogenetic Compounds in Preclinical Murine Models

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1604 ◽  
Author(s):  
Giovanni Luca Gravina ◽  
Andrea Mancini ◽  
Alessandro Colapietro ◽  
Simona Delle Monache ◽  
Roberta Sferra ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Tumor Cells ◽  
Kinase Inhibitor ◽  
Vasculogenic Mimicry ◽  
Disease Free Survival ◽  
Therapeutic Effects ◽  
Murine Models ◽  
Tubule Formation

Background. Glioblastoma multiforme (GBM) is a devastating disease showing a very poor prognosis. New therapeutic approaches are needed to improve survival and quality of life. GBM is a highly vascularized tumor and as such, chemotherapy and anti-angiogenic drugs have been combined for treatment. However, as treatment-induced resistance often develops, our goal was to identify and treat pathways involved in resistance to treatment to optimize the treatment strategies. Anti-angiogenetic compounds tested in preclinical and clinical settings demonstrated recurrence associated to secondary activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway. Aims. Here, we determined the sensitizing effects of the small molecule and oral available dual TORC1/TORC2 dissociative inhibitor, RES529, alone or in combination with the anti-VEGF blocking antibody, bevacizumab, or the tyrosine kinase inhibitor, sunitinib, in human GBM models. Results. We observed that RES529 effectively inhibited dose-dependently the growth of GBM cells in vitro counteracting the insurgence of recurrence after bevacizumab or sunitinib administration in vivo. Combination strategies were associated with reduced tumor progression as indicated by the analysis of Time to Tumor Progression (TTP) and disease-free survival (DSF) as well as increased overall survival (OS) of tumor bearing mice. RES529 was able to reduce the in vitro migration of tumor cells and tubule formation from both brain-derived endothelial cells (angiogenesis) and tumor cells (vasculogenic mimicry). Conclusions. In summary, RES529, the first dual TORC1/TORC2 dissociative inhibitor, lacking affinity for ABCB1/ABCG2 and having good brain penetration, was active in GBM preclinical/murine models giving credence to its use in clinical trial for patients with GBM treated in association with anti-angiogenetic compounds.

scholarly journals Estrogen receptor β1 exerts antitumoral effects on SK-OV-3 ovarian cancer cells

2007 ◽  
Vol 193 (3) ◽  
pp. 421-433 ◽  
Author(s):  
Oliver Treeck ◽  
Georg Pfeiler ◽  
Diana Mitter ◽  
Claus Lattrich ◽  
Gerhard Piendl ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Cellular Proliferation ◽  
Kinase Inhibitor ◽  
Splice Variants ◽  
Ovarian Cancer Cell Line ◽  
Regulation Of Gene Expression ◽  
Ovarian Cancer Cells ◽  
Mrna Levels

Estrogen receptor (ER) β1 and its splice variants are expressed both in ovary and ovarian cancer. We studied the role of ERβ1 and two of its splice variants in regulation of gene expression, cellular proliferation, apoptosis, and migration of an ovarian cancer cell line. In this study, we transfected SK-OV-3 ovarian cancer cells with vectors coding for ERβ1 or its splice variants ERβ-δ125 and ERβ-δ1256, and tested their response to estrogen and tamoxifen in comparison with the untransfected cells. Heterologous expression of ERβ1, but not of the exon-deleted ERβ variants resulted in notably slower cell growth of SK-OV-3 ovarian cancer cells, an effect accompanied by more than tenfold increase of cyclin-dependent kinase inhibitor p21(WAF1) transcript levels and a significant reduction of cyclin A2 mRNA levels. SK-OV-3 cells stably overexpressing ERβ1 ligand independently also exhibited an increased apoptosis rate and a significantly decreased motility, an effect accompanied by upregulation of fibulin 1c. Our data demonstrate that ERβ1, but not the exon-deleted isoforms tested exerts multiple antitumoral effects on SK-OV-3 ovarian cancer cells even in the absence of estradiol or functional ERα.

scholarly journals Metabolic Reprogramming in Thyroid Cancer: Role of the Epithelial-Mesenchymal Transition

Endocrines ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 427-438
Author(s):  
Monica Fedele ◽  
Sabrina Battista ◽  
Laura Cerchia
Keyword(s):  
Thyroid Cancer ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Cellular Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Anaplastic Thyroid Carcinoma ◽  
Metabolic Changes ◽  
Metabolic Reprogramming ◽  
Mesenchymal Transition

Thyroid cancer (TC) represents the most common endocrine malignancy, with an increasing incidence all over the world. Papillary TC (PTC), a differentiated TC subtype, is the most common and, even though it has an excellent prognosis following radioiodine (RAI) ablation, it shows an aggressive behavior in 20–30% of cases, becoming RAI-resistant and/or metastatic. On the other side, anaplastic thyroid carcinoma (ATC), the most undifferentiated TC, is a rare but devastating disease, indicating that progression of differentiated to undifferentiated forms of TC could be responsible for RAI-resistance and increased mortality. The epithelial-to-mesenchymal transition (EMT) plays a pivotal role in both tumor progression and resistance to therapy. Moreover, during tumor progression, cancer cells modify their metabolism to meet changed requirements for cellular proliferation. Through these metabolic changes, cancer cells may adopt cancer stem cell-like properties and express an EMT phenotype. EMT, in turn, can induce metabolic changes to which cancer cells become addicted. Here we review metabolic reprogramming in TC highlighting the role of EMT with the aim to explore a potential field to find out new therapeutic strategies for advanced-stage PTC. Accordingly, we discuss the identification of the metabolic enzymes and metabolites, critical to TC progression, which can be employed either as predicting biomarkers of tumor response to RAI therapy or possible targets in precision medicine.

Lupeol Inhibits Proliferation and Promotes Apoptosis of Ovarian Cancer Cells by Inactivating Phosphoinositide-3-Kinase/Protein Kinase B/ Mammalian Target of Rapamycin Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 206-210
Author(s):  
Feng Chen ◽  
Bei Zhang
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Protein Kinase ◽  
Cell Viability ◽  
Cancer Cells ◽  
Protein Kinase B ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Ovarian Cancer Cells ◽  
Phosphoinositide 3 Kinase

Lupeol exhibits multiple pharmacological activities including, anticancerous, anti-inflammatory, and antioxidant. The aim of this study was to explore the anticancerous activity of lupeol on ovarian cancer cells and examine its mechanism of action. To this end, increasing concentrations of lupeol on cell viability, cell cycle, and apoptosis in Caov-3 cells were evaluated. Lupeol inhibited cell viability, induced G1 phase arrest in cell cycle, increased cell apoptosis, and inhibited the ratio of phospho-Akt/protein kinase B and phospho-mammalian target of rapamycin/mammalian target of rapamycin. In conclusion, these data suggest that lupeol may play a therapeutic role in ovarian cancer.

Silencing STAT3 enhances sensitivity of cancer cells to doxorubicin and inhibits tumor progression

Life Sciences ◽  
2021 ◽  
Vol 275 ◽  
pp. 119369
Author(s):  
Navneet Joshi ◽  
Farnaz Hajizadeh ◽  
Ehsan Ansari Dezfouli ◽  
Angelina Olegovna Zekiy ◽  
Mohsen Nabi Afjadi ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Cancer Cells

scholarly journals Tumor-associated macrophages: potential therapeutic strategies and future prospects in cancer

2021 ◽  
Vol 9 (1) ◽  
pp. e001341
Author(s):  
Chunxiao Li ◽  
Xiaofei Xu ◽  
Shuhua Wei ◽  
Ping Jiang ◽  
Lixiang Xue ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
Tumor Immunotherapy ◽  
Therapeutic Strategies ◽  
Preclinical Studies ◽  
Future Prospects ◽  
Tumor Associated Macrophages

Macrophages are the most important phagocytes in vivo. However, the tumor microenvironment can affect the function and polarization of macrophages and form tumor-associated macrophages (TAMs). Usually, the abundance of TAMs in tumors is closely associated with poor prognosis. Preclinical studies have identified important pathways regulating the infiltration and polarization of TAMs during tumor progression. Furthermore, potential therapeutic strategies targeting TAMs in tumors have been studied, including inhibition of macrophage recruitment to tumors, functional repolarization of TAMs toward an antitumor phenotype, and other therapeutic strategies that elicit macrophage-mediated extracellular phagocytosis and intracellular destruction of cancer cells. Therefore, with the increasing impact of tumor immunotherapy, new antitumor strategies to target TAMs are now being discussed.

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