scholarly journals Glutathione S‐transferase Pi 1 is a valuable predictor for cancer drug resistance in esophageal squamous cell carcinoma

2018 ◽  
Vol 110 (2) ◽  
pp. 795-804 ◽  
Author(s):  
Shinpei Ogino ◽  
Hirotaka Konishi ◽  
Daisuke Ichikawa ◽  
Daiki Matsubara ◽  
Katsutoshi Shoda ◽  
...  
Author(s):  
Wei Cui ◽  
Tingting Fang ◽  
Zhaoheng Duan ◽  
Dongfang Xiang ◽  
Yanxia Wang ◽  
...  

Platinum-based regimens have been routinely used in the clinical treatment of patients with esophageal squamous cell carcinoma (ESCC). However, administration of these drugs is frequently accompanied by drug resistance. Revealing the underlying mechanisms of the drug resistance and developing agents that enhance the sensitivity to platinum may provide new therapeutic strategies for the patients. In the present study, we found that the poor outcome of ESCC patients receiving platinum-based regimens was associated with co-expression of Shh and Sox2. The sensitivity of ESCC cell lines to cisplatin was related to their activity of Shh signaling. Manipulating of Shh expression markedly changed the sensitivity of ESCC cells to platinum. Continuous treatment with cisplatin resulted in the activation of Shh signaling and enhanced cancer stem cell-like phenotypes in ESCC cells. Dihydroartemisinin (DHA), a classic antimalarial drug, was identified as a novel inhibitor of Shh pathway. Treatment with DHA attenuated the cisplatin-induced activation of the Shh pathway in ESCC cells and synergized the inhibitory effect of cisplatin on proliferation, sphere and colony formation of ALDH-positive ESCC cells in vitro and growth of ESCC cell-derived xenograft tumors in vivo. Taken together, these results demonstrate that the Shh pathway is an important player in cisplatin-resistant ESCC and DHA acts as a promising therapeutic agent to sensitize ESCC to cisplatin treatment.


2020 ◽  
Vol 10 ◽  
Author(s):  
Lili Duan ◽  
Jiaojiao Ma ◽  
Wanli Yang ◽  
Lu Cao ◽  
Xiaoqian Wang ◽  
...  

2019 ◽  
Vol 26 (13) ◽  
pp. 4814-4825
Author(s):  
Yosuke Ooizumi ◽  
Keita Kojima ◽  
Kazuharu Igarashi ◽  
Yoko Tanaka ◽  
Hiroki Harada ◽  
...  

2020 ◽  
Author(s):  
Wei Cui ◽  
Tingting Fang ◽  
Zhaoheng Duan ◽  
Dongfang Xiang ◽  
Yanxia Wang ◽  
...  

Abstract Background: Platinum-based regimens have been routinely used in the clinical treatment of patients with esophageal squamous cell carcinoma (ESCC). However, administration of these drugs is frequently accompanied by drug resistance. Revealing the underlying mechanisms of the drug resistance and developing agents that enhance the sensitivity to platinum may provide new therapeutic strategies for the patients. Methods: Immunohistochemistry, western blotting, RT-PCR, flow cytometry and immunofluorescence microscopy were used to detect the expression of Shh pathway members and cancer stem cell(CSC) biomarkers in ESCC specimens and cell lines. Functional assays, including MTT, tumorsphere formation assay, RTCA and an in vivo tumour growth assay, were conducted to assess the effect of Dihydroartemisinin (DHA) on the proliferation and renewal ability of ESCC cells. HPLC was used to examine the concention of cisplatin in ESCC cells.Results: We found that the poor outcome of ESCC patients receiving platinum-based regimens was associated with co-expression of Shh and Sox2. The sensitivity of ESCC cell lines to cisplatin was related to their activity of Shh signaling. Manipulating of Shh expression markedly changed the sensitivity of ESCC cells to platinum. Continuous treatment with cisplatin resulted in the activation of Shh signaling and enhanced cancer stem cell-like phenotypes in ESCC cells. DHA, a classic antimalarial drug, was identified as a novel inhibitor of Shh pathway. Treatment with DHA attenuated the cisplatin-induced activation of the Shh pathway in ESCC cells and synergized the inhibitory effect of cisplatin on proliferation, sphere and colony formation of ALDH-positive ESCC cells in vitro and growth of ESCC cell-derived xenograft tumors in vivo. Conclusion: These results demonstrate that the Shh pathway is an important player in cisplatin-resistant ESCC and DHA acts as a promising therapeutic agent to sensitize ESCC to cisplatin treatment.


2019 ◽  
Vol 51 (8) ◽  
pp. 826-833 ◽  
Author(s):  
Zhenghua Zhang ◽  
Ran Xiong ◽  
Caiwei Li ◽  
Meiqing Xu ◽  
Mingfa Guo

AbstractEsophageal squamous cell carcinoma (ESCC) is a common malignancy with poor prognosis. The drug resistance compromises the efficacy of chemotherapy for ESCC. Long non-coding RNA taurine upregulated gene 1 (TUG1) has been identified as a promoter of cancer progression and chemotherapy resistance in many malignancies. However, the exact role of TUG1 in ESCC chemotherapy resistance remains unclear. In this study, we showed that TUG1 expression in TE-1-derived cisplatin (DDP)-resistant (TE-1/DDP) cells was higher than that in TE-1 cells. Furthermore, TUG1 promoted DDP resistance in TE-1 and TE-1/DDP cells by promoting cell proliferation, suppressing cell apoptosis, and elevating protein expression of the classical multi-drug resistance-related P-gp. In contrast, TUG1 knockdown exerted an opposite effect. Mechanistically, RNA pull-down and RNA immunoprecipitation assays confirmed that TUG1 directly bound to nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein and elevated Nrf2 protein expression. Moreover, Nrf2-neutralizing antibody effectively reversed the TUG1 overexpression-mediated promotion of ESCC cell resistance to DDP. In conclusion, our findings demonstrated that TUG1 promoted ESCC cell resistance to DDP, at least in part, through upregulating Nrf2.


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