scholarly journals ClC-3/SGK1 regulatory axis enhances the olaparib-induced antitumor effect in human stomach adenocarcinoma

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Zhuoyu Gu ◽  
Liping Wang ◽  
Xiaohan Yao ◽  
Qian Long ◽  
Kaping Lee ◽  
...  
Keyword(s):  
Cell Growth ◽  
Antitumor Effect ◽  
Therapeutic Potential ◽  
Parp Inhibitor ◽  
Akt Pathway ◽  
Enhancement Effect ◽  
Migration Inhibition ◽  
Cell Growth And Migration ◽  
Stomach Adenocarcinoma ◽  
And Migration

Abstract Currently, only a few available targeted drugs are considered to be effective in stomach adenocarcinoma (STAD) treatment. The PARP inhibitor olaparib is a molecularly targeted drug that continues to be investigated in BRCA-mutated tumors. However, in tumors without BRCA gene mutations, particularly in STAD, the effect and molecular mechanism of olaparib are unclear, which largely restricts the use of olaparib in STAD treatment. In this study, the in vitro results showed that olaparib specifically inhibited cell growth and migration, exerting antitumor effect in STAD cell lines. In addition, a ClC-3/SGK1 regulatory axis was identified and validated in STAD cells. We then found that the down-regulation of ClC-3/SGK1 axis attenuated olaparib-induced cell growth and migration inhibition. On the contrary, the up-regulation of ClC-3/SGK1 axis enhanced olaparib-induced cell growth and migration inhibition, and the enhancement effect could be attenuated by SGK1 knockdown. Consistently, the whole-cell recorded chloride current activated by olaparib presented the same variation trend. Next, the clinical data showed that ClC-3 and SGK1 were highly expressed in human STAD tissues and positively correlated (r = 0.276, P = 0.009). Furthermore, high protein expression of both ClC-3 (P = 0.030) and SGK1 (P = 0.006) was associated with poor survival rate in STAD patients, and positive correlations between ClC-3/SGK1 and their downstream molecules in STAD tissues were demonstrated via the GEPIA datasets. Finally, our results suggested that olaparib inhibited the PI3K/AKT pathway in STAD cells, and up-regulation of ClC-3/SGK1 axis enhanced olaparib-induced PI3K/AKT pathway inhibition. The animal experiments indicated that olaparib also exerted antitumor effect in vivo. Altogether, our findings illustrate that olaparib exerts antitumor effect in human STAD, and ClC-3/SGK1 regulatory axis enhances the olaparib-induced antitumor effect. Up-regulation of the ClC-3/SGK1 axis may provide promising therapeutic potential for the clinical application of olaparib in STAD treatment.

Cell-growth and migration inhibition of human mesothelioma cells induced by 3-O-Methylfunicone from Penicillium pinophilum and cisplatin

2011 ◽  
Vol 30 (4) ◽  
pp. 1343-1351 ◽  
Author(s):  
Elisabetta Buommino ◽  
Anna De Filippis ◽  
Rosario Nicoletti ◽  
Massimo Menegozzo ◽  
Simona Menegozzo ◽  
...  
Keyword(s):  
Cell Growth ◽  
Migration Inhibition ◽  
Cell Growth And Migration ◽  
Penicillium Pinophilum ◽  
And Migration

ROR1 contributes to melanoma cell growth and migration by regulating N-cadherin expression via the PI3K/Akt pathway

2015 ◽  
Vol 55 (11) ◽  
pp. 1772-1785 ◽  
Author(s):  
Natalia Brenda Fernández ◽  
Daniela Lorenzo ◽  
María Elisa Picco ◽  
Gastón Barbero ◽  
Leonardo Sebastián Dergan-Dylon ◽  
...  
Keyword(s):  
Cell Growth ◽  
Melanoma Cell ◽  
Akt Pathway ◽  
Cell Growth And Migration ◽  
And Migration

scholarly journals Overexpression of WDFY2 inhibits prostate cancer cell growth and migration via inactivation of Akt pathway

Tumor Biology ◽  
2017 ◽  
Vol 39 (6) ◽  
pp. 101042831770482 ◽  
Author(s):  
Jianqing Wang ◽  
Xu Chen ◽  
Shijun Tong ◽  
Huihui Zhou ◽  
Jianliang Sun ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Akt Pathway ◽  
Cancer Cell Growth ◽  
Cell Growth And Migration ◽  
And Migration

Knockout of Ajuba Attenuates the Growth and Migration of Hepatocellular Carcinoma Cells

2020 ◽  
Vol 160 (11-12) ◽  
pp. 650-658
Author(s):  
Yichen Le ◽  
Yi He ◽  
Meirong Bai ◽  
Ying Wang ◽  
Jiaxue Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Cancer Progression ◽  
Normal Liver ◽  
Cell Growth And Migration ◽  
And Migration ◽  
Hcc Cells

Ajuba has been found to be mutated or aberrantly regulated in several human cancers and plays important roles in cancer progression via different signaling pathways. However, little is known about the role of Ajuba in hepatocellular carcinoma (HCC). Here, we found an upregulation of Ajuba expression in HCC tissues compared with normal liver tissues, while a poor prognosis was observed in HCC patients with high Ajuba expression. Knockout of Ajuba in HCC cells inhibited cell growth in vitro and in vivo, suppressed cell migration, and enhanced the cell apoptosis under stress. Moreover, re-expression of Ajuba in Ajuba-deficient cells could restore the phenotype of Ajuba-deficient cells. In conclusion, these results indicate that Ajuba is upregulated in HCC and promotes cell growth and migration of HCC cells, suggesting that Ajuba could possibly be a new target for HCC diagnosis and treatment.

scholarly journals Development of a Decellularized Porcine Esophageal Matrix for Potential Applications in Cancer Modeling

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1055
Author(s):  
Hersh Chaitin ◽  
Michael L. Lu ◽  
Michael B. Wallace ◽  
Yunqing Kang
Keyword(s):  
Cell Growth ◽  
Lymphatic Vessels ◽  
Significant Loss ◽  
Cancer Cell Growth ◽  
Cell Growth And Migration ◽  
Decellularized Extracellular Matrix ◽  
Cancer Models ◽  
The Matrix ◽  
Potential Applications ◽  
And Migration

Many decellularized extracellular matrix-derived whole organs have been widely used in studies of tissue engineering and cancer models. However, decellularizing porcine esophagus to obtain decellularized esophageal matrix (DEM) for potential biomedical applications has not been widely investigated. In this study a modified decellularization protocol was employed to prepare a porcine esophageal DEM for the study of cancer cell growth. The cellular removal and retention of matrix components in the porcine DEM were fully characterized. The microstructure of the DEM was observed using scanning electronic microscopy. Human esophageal squamous cell carcinoma (ESCC) and human primary esophageal fibroblast cells (FBCs) were seeded in the DEM to observe their growth. Results show that the decellularization process did not cause significant loss of mechanical properties and that blood ducts and lymphatic vessels in the submucosa layer were also preserved. ESCC and FBCs grew on the DEM well and the matrix did not show any toxicity to cells. When FBS and ESCC were cocultured on the matrix, they secreted more periostin, a protein that supports cell adhesion on matrix. This study shows that the modified decellularization protocol can effectively remove the cell materials and maintain the microstructure of the porcine esophageal matrix, which has the potential application of studying cell growth and migration for esophageal cancer models.

scholarly journals Downregulation of miR-193a-3p inhibits cell growth and migration in renal cell carcinoma by targeting PTEN

Tumor Biology ◽  
2017 ◽  
Vol 39 (6) ◽  
pp. 101042831771195 ◽  
Author(s):  
Lingqi Liu ◽  
Yanqin Li ◽  
Shuchao Liu ◽  
Qixin Duan ◽  
Liang Chen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Growth ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Growth And Migration ◽  
And Migration
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