513 Synergistic inhibition of ovarian and endometrial cancer cell lines using combined treatment of ARQ 092 and ARQ 087 in vitro and in vivo

2014 ◽  
Vol 50 ◽  
pp. 167 ◽  
Author(s):  
Y. Yu ◽  
E. Nakuci ◽  
E. Chiesa ◽  
C.R. Chen ◽  
E. Marchlik ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Combined Treatment ◽  
Cancer Cell Lines ◽  
Endometrial Cancer Cell ◽  
Synergistic Inhibition

Variances in the Expression Profile of the EMT-Related Genes in Endometrial Cancer Lines In Vitro Study

2021 ◽  
Vol 22 ◽  
Author(s):  
Robert Nowakowski ◽  
Beniamin Grabarek ◽  
Anna Burnat-Olech ◽  
Dariusz Boroń ◽  
Monika Paul-Samojedny
Keyword(s):  
Endometrial Cancer ◽  
Expression Pattern ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Cultures ◽  
Expression Profile ◽  
Histological Grade ◽  
Cancer Cell Lines ◽  
Endometrial Cancer Cell

Background: This study aimed to evaluate the variances in the expression pattern of mRNAs and miRNAs related to the EMT in the Ishikawa (histological grade 1; G1), EC-1A (histological grade 2; G2), and KLE (histological grade 3; G3) cell cultures under cisplatin treatment. Methods: Endometrial cancer cell lines were exposed to 75.22 mg (an average concentration of the drug used in patients with endometrial cancer) for 12.24 and 48 hours compared to the untreated cells (control). The molecular analysis included extraction of total RNA, microarray analysis (mRNA and miRNA), RTqPCR, and the ELISA assay. Results: Out of 226 mRNAs associated with the EMT, the number of mRNAs differentially expressed in endometrial cancer cell cultures treated with cisplatin compared to a control culture was as follows: Ishikawa line - 87 mRNAs; EC-1A - 84 mRNAs; KLE - 71 mRNAs (p<0.05). The greatest changes in the Ishikawa line treated with the drug compared to the control were noticed for mRNA STAT1 TGFβ1, SMAD3, FOXO8, whereas in EC-1A, they were mRNA TGFβ1, BAMBI, SMAD4, and in KLE mRNA COL1A1, FOXO8, TGFβ1. The analysis also showed that miR-106a, miR-30d, miR-300 are common for all cell lines used in this experiment. Conclusion: Cisplatin changes the expression profile of genes associated with EMT in endometrial cancer cell lines. It seems that the expression pattern of TGFβ1 might be a promising, supplementary molecular marker of the effectiveness of cisplatin therapy. The analysis showed that miR-30d, miR-300, and miR-106a are involved in the regulation of the expression of EMT-related genes.

scholarly journals Utility and Mechanism of SHetA2 and Paclitaxel for Treatment of Endometrial Cancer

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2322
Author(s):  
Vishal Chandra ◽  
Rajani Rai ◽  
Doris Mangiaracina Benbrook
Keyword(s):  
Cell Cycle ◽  
Endometrial Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Recurrence Risk ◽  
Cancer Cell Lines ◽  
Tumor Growth Inhibition ◽  
Endometrial Cancer Cell ◽  
Atp Production

Endometrial cancer patients with advanced disease or high recurrence risk are treated with chemotherapy. Our objective was to evaluate the utility and mechanism of a novel drug, SHetA2, alone and in combination with paclitaxel, in endometrial cancer. SHetA2 targets the HSPA chaperone proteins, Grp78, hsc70, and mortalin, which have high mutation rates in endometrial cancer. SHetA2 effects on cancerous phenotypes, mitochondria, metabolism, protein expression, mortalin/client protein complexes, and cell death were evaluated in AN3CA, Hec13b, and Ishikawa endometrial cancer cell lines, and on growth of Ishikawa xenografts. In all three cell lines, SHetA2 inhibited anchorage-independent growth, migration, invasion, and ATP production, and induced G1 cell cycle arrest, mitochondrial damage, and caspase- and apoptosis inducing factor (AIF)-mediated apoptosis. These effects were associated with altered levels of proteins involved in cell cycle regulation, mitochondrial function, protein synthesis, endoplasmic reticulum stress, and metabolism; disruption of mortalin complexes with mitochondrial and metabolism proteins; and inhibition of oxidative phosphorylation and glycolysis. SHetA2 and paclitaxel exhibited synergistic combination indices in all cell lines and exerted greater xenograft tumor growth inhibition than either drug alone. SHetA2 is active against endometrial cancer cell lines in culture and in vivo and acts synergistically with paclitaxel.

Silencing of ghrelin receptor expression inhibits endometrial cancer cell growth in vitro and in vivo

2013 ◽  
Vol 305 (2) ◽  
pp. E305-E313 ◽  
Author(s):  
Jenny N. T. Fung ◽  
Penny L. Jeffery ◽  
John D. Lee ◽  
Inge Seim ◽  
Deborah Roche ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Gene Silencing ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Endometrial Cancer Cell ◽  
Mouse Xenograft ◽  
Ghrelin Receptor

Ghrelin is a 28-amino acid peptide hormone produced predominantly in the stomach but also in a range of normal cell types and tumors, where it has endocrine, paracrine, and autocrine roles. Previously, we have demonstrated that ghrelin has proliferative and antiapoptotic effects in endometrial cancer cell lines, suggesting a potential role in promoting tumor growth. In the present study, we investigated the effect of ghrelin receptor, GHSR, and gene silencing in vitro and in vivo and characterized ghrelin and GHSR1a protein expression in human endometrial tumors. GHSR gene silencing was achieved in the Ishikawa and KLE endometrial cancer cell lines, using a lentiviral short-hairpin RNA targeting GHSR. The effects of GHSR1a knockdown were further analyzed in vivo using the Ishikawa cell line in a NOD/SCID xenograft model. Cell proliferation was reduced in cultured GHSR1a knockdown Ishikawa and KLE cells compared with scrambled controls in the absence of exogenously applied ghrelin and in response to exogenous ghrelin (1,000 nM). The tumor volumes were reduced significantly in GHSR1a knockdown Ishikawa mouse xenograft tumors compared with scrambled control tumours. Using immunohistochemistry, we demonstrated that ghrelin and GHSR1a are expressed in benign and cancerous glands in human endometrial tissue specimens, although there was no correlation between the intensity of staining and cancer grade. These data indicate that downregulation of GHSR expression significantly inhibits endometrial cancer cell line and mouse xenograft tumour growth. This is the first preclinical evidence that downregulation of GHSR may be therapeutic in endometrial cancer.

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