scholarly journals EF24 induces ROS-mediated apoptosis via targeting thioredoxin reductase 1 in gastric cancer cells

Oncotarget ◽  
2016 ◽  
Vol 7 (14) ◽  
pp. 18050-18064 ◽  
Author(s):  
Peng Zou ◽  
Yiqun Xia ◽  
Weiqian Chen ◽  
Xi Chen ◽  
Shilong Ying ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Thioredoxin Reductase ◽  
Gastric Cancer Cells ◽  
Thioredoxin Reductase 1

scholarly journals Ethaselen synergizes with oxaliplatin in tumor growth inhibition by inducing ROS production and inhibiting TrxR1 activity in gastric cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Haiyong Zhang ◽  
Jing Wu ◽  
Jinqiu Yuan ◽  
Huafu Li ◽  
Yawei Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Nude Mice ◽  
Combined Treatment ◽  
Thioredoxin Reductase ◽  
Tumor Growth Inhibition ◽  
Gastric Cancer Cells

Abstract Background Oxaliplatin is one of the most commonly used chemotherapeutic agent for the treatment of various cancers, including gastric cancer. It has, however, a narrow therapeutic index due to its toxicity and the occurrence of drug resistance. Hence, it is of great significance to develop novel therapies to potentiate the anti-tumor effect and reduce the toxicity of oxaliplatin. In our previous study, we demonstrated that ethaselen (BBSKE), an inhibitor of thioredoxin reductase, effectively inhibited the growth of gastric cancer cells and promoted apoptosis in vitro. In the present study, we investigated whether BBSKE can potentiate the anti-tumor effect of oxaliplatin in gastric cancer in vivo and vitro. Methods Cellular apoptosis and ROS levels were analyzed by flow cytometry. Thioredoxin reductase 1 (TrxR1) activity in gastric cancer cells, organoid and tumor tissues was determined by using the endpoint insulin reduction assay. Western blot was used to analyze the expressions of the indicated proteins. Nude mice xenograft models were used to test the effects of BBSKE and oxaliplatin combinations on gastric cancer cell growth in vivo. In addition, we also used the combined treatment of BBSKE and oxaliplatin in three cases of gastric cancer Patient-Derived organoid (GC-PDO) to detect the anti-tumor effect. Results We found that BBSKE significantly enhanced oxaliplatin-induced growth inhibition in gastric cancer cells by inhibiting TrxR1 activity. Because of the inhibition of TrxR1 activity, BBSKE synergized with oxaliplatin to enhance the production of ROS and activate p38 and JNK signaling pathways which eventually induced apoptosis of gastric cancer cells. In vivo, we also found that BBSKE synergized with oxaliplatin to suppress the gastric cancer tumor growth in xenograft nude mice model, accompanied by the reduced TrxR1 activity. Remarkably, we found that BBSKE attenuated body weight loss evoked by oxaliplatin treatment. We also used three cases of GC-PDO and found that the combined treatment of BBSKE and oxaliplatin dramatically inhibited the growth and viability of GC-PDO with increased ROS level, decreased TrxR1 activity and enhanced apoptosis. Conclusions This study elucidates the underlying mechanisms of synergistic effect of BBSKE and oxaliplatin, and suggests that the combined treatment has potential value in gastric cancer therapy.

Alpha-fetoprotein producing gastric cancer cells lack transcription factor AT-motif binding factor 1 (ATBF1)

2001 ◽  
Vol 120 (5) ◽  
pp. A31-A31
Author(s):  
H KATAOKA ◽  
T JOH ◽  
T OHSHIMA ◽  
Y ITOH ◽  
K SENOO ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Alpha Fetoprotein ◽  
Gastric Cancer Cells ◽  
Binding Factor

Distinct mechanism of helicobacter pylori-mediated NF-κB activation between gastric cancer cells, MKN45 and monocystic cells, THP-1

2001 ◽  
Vol 120 (5) ◽  
pp. A82-A82 ◽  
Author(s):  
S MAEDA ◽  
Y MITSUNO ◽  
Y HIRATA ◽  
M AKANUMA ◽  
H YOSHIDA ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cancer Cells ◽  
Gastric Cancer Cells ◽  
Distinct Mechanism

Hepatocyte Growth Factor Promotes Cell Survival by Phosphorylation of BAD in Gastric Cancer Cells

2008 ◽  
Vol 17 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Kyung Hee Lee ◽  
Eun Young Choi ◽  
Min Kyoung Kim ◽  
Myung Soo Hyun ◽  
Jong Ryul Eun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cell Survival ◽  
Cancer Cells ◽  
Gastric Cancer Cells ◽  
Hepatocyte Growth

Silencing of circRACGAP1 Sensitizes Gastric Cancer Cells to Apatinib via Modulating Autophagy by Targeting miR-3657 and ATG7

2019 ◽  
Author(s):  
Ling Ma ◽  
Zhangding Wang ◽  
Mengyan Xie ◽  
Weiyou Zhu ◽  
Fengming Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Gastric Cancer Cells

Effects and Mechanisms of Anlotinib and Dihydroartemisinin Combination Therapy in Ameliorating Malignant Biological Behavior of Gastric Cancer Cells

2020 ◽  
Vol 21 ◽  
Author(s):  
Qiong Luo ◽  
Suyun Zhang ◽  
Donghuan Zhang ◽  
Rui Feng ◽  
Nan Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Chorioallantoic Membrane ◽  
Cell Counting ◽  
Biological Behavior ◽  
Gastric Cancer Cells ◽  
Invasion And Migration ◽  
Apoptosis Related Protein ◽  
And Migration

Background: Gastric cancer(GC) is currently one of the major malignancies that threatens human lives and health. Anlotinib is a novel small-molecule that inhibits angiogenesis to exert anti-tumor effects. However, the function in gastric cancer is incompletely understood. Objective: The aim of the present study was to investigate the anti-tumor effects and molecular mechanisms of anlotinib combined with dihydroartemisinin (DHA) in SGC7901 gastric cancer cells. Method: Different concentrations of anlotinib and DHA were used to treat SGC7901 gastric cancer cells, after which cell proliferation was measured. Drug interactions of anlotinib and DHA were analyzed by the Chou-Talalay method with CompuSyn software. proliferation, apoptosis, invasion, migration, and angiogenesis were measured using the cell counting kit-8 (CCK8) assay, flow cytometry, Transwell invasion assays, scratch assays, and chicken chorioallantoic membrane (CAM) assays. proliferation-associated protein (Ki67), apoptosis-related protein (Bcl-2), and vascular endothelial growth factor A (VEGF-A) were quantified by Western bloting. Results: The combination of 2.5 μmol/L of anlotinib and 5 of μmol/L DHA was highly synergistic in inhibiting cell growth, significantly increased the apoptosis rate and suppressed obviously the invasion and migration capability and angiogenesis of gastric cancer cells. In addition, the expression levels of Ki67, Bcl-2, and VEGF-A, as well as angiogenesis, were significantly decreased in the Combination of drugs compared with in control and either drug alone. Conclusion: The combination of anlotinib and DHA showed synergistic antitumor activity, suggesting their potential in treating patients with gastric cancer.

OSI-027 alleviates oxaliplatin chemoresistance in gastric cancer cells by suppressing P-gp induction

2020 ◽  
Vol 20 ◽  
Author(s):  
En Xu ◽  
Hao Zhu ◽  
Feng Wang ◽  
Ji Miao ◽  
Shangce Du ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Cell Counting ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Dual Inhibitor ◽  
Induced Apoptosis

: Gastric cancer is one of the most common malignancies worldwide and the third leading cause of cancer-related death. In the present study, we investigated the potential activity of OSI-027, a potent and selective mammalian target of rapamycin complex 1/2 (mTOR1/2) dual inhibitor, alone or in combination with oxaliplatin against gastric cancer cells in vitro. Cell counting kit-8 assays and EdU staining were performed to examine the proliferation of cancer cells. Cell cycle and apoptosis were detected by flow cytometry. Western blot was used to detect the elements of the mTOR pathway and Pgp in gastric cancer cell lines. OSI-027 inhibited the proliferation of MKN-45 and AGS cells by arresting the cell cycle in the G0/G1 phase. At the molecular level, OSI-027 simultaneously blocked mTORC1 and mTORC2 activation, and resulted in the downregulation of phosphor-Akt, phpspho-p70S6k, phosphor-4EBP1, cyclin D1, and cyclin-dependent kinase4 (CDK4). Additionally, OSI-027 also downregulated P-gp, which enhanced oxaliplatin-induced apoptosis and suppressed multidrug resistance. Moreover, OSI-027 exhibited synergistic cytotoxic effects with oxaliplatin in vitro, while a P-gp siRNA knockdown significantly inhibited the synergistic effect. In summary, our results suggest that dual mTORC1/mTORC2 inhibitors (e.g., OSI-027) should be further investigated as a potential valuable treatment for gastric cancer.

Sign in / Sign up

Export Citation Format

Share Document