scholarly journals A thioredoxin reductase inhibitor ethaselen induces growth inhibition and apoptosis in gastric cancer

2020 ◽  
Vol 11 (10) ◽  
pp. 3013-3019
Author(s):  
Wang Wu ◽  
Zhiying Yang ◽  
Xing Xiao ◽  
Tailai An ◽  
Bo Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Inhibition ◽  
Reductase Inhibitor ◽  
Thioredoxin Reductase

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.

scholarly journals Transduced caudal‐type homeobox ( CDX ) 2/ CDX 1 can induce growth inhibition on CDX ‐deficient gastric cancer by rapid intestinal differentiation

2018 ◽  
Vol 109 (12) ◽  
pp. 3853-3864 ◽  
Author(s):  
Chiemi Nakayama ◽  
Nobutake Yamamichi ◽  
Shuta Tomida ◽  
Yu Takahashi ◽  
Natsuko Kageyama‐Yahara ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Inhibition ◽  
Intestinal Differentiation ◽  
Induce Growth Inhibition

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 PTEN/MMAC1 enhances the growth inhibition by anticancer drugs with downregulation of IGF-II expression in gastric cancer cells

2005 ◽  
Vol 37 (5) ◽  
pp. 391-398 ◽  
Author(s):  
Pyoung Han Hwang ◽  
Sun Young Kim ◽  
Jung Chang Lee ◽  
Sun Jun Kim ◽  
Ho Keun Yi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Gastric Cancer Cells

scholarly journals Underexpressed CNDP2 Participates in Gastric Cancer Growth Inhibition through Activating the MAPK Signaling Pathway

2013 ◽  
Vol 20 (1) ◽  
pp. 17-28 ◽  
Author(s):  
Zhenwei Zhang ◽  
Lei Miao ◽  
Xiaoming Xin ◽  
Jianpeng Zhang ◽  
Shengsheng Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Inhibition ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Cancer Growth
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