Tunicamycin specifically aggravates ER stress and overcomes chemoresistance in multidrug-resistant gastric cancer cells by inhibiting N-glycosylation

Wu, Jian; Chen, Sheng; Líu, Hao; Zhang, Zhe; Zhen, Ni; Chen, Jie; Yang, Zhiping; Nie, Yongzhan; Fan, Daiming

doi:10.1186/s13046-018-0935-8

Cited by 140 publications

(120 citation statements)

References 63 publications

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“…Furthermore, some analysis revealed ATGs were differentially enriched in platinum resistance. Research has demonstrated that a combination of inhibitors in GC improves cisplatin resistance [26][27][28] , which is consistent and concurs with our results. ATGs can promote progress in GC disease progress through platinum resistance.…”

Section: Discussionsupporting

confidence: 93%

Prognostic Autophagy-Related Genes of Gastric Cancer Patients on Chemotherapy

Liu

et al. 2020

Preprint

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Background, Chemotherapy resistance based on the use of fluorouracil and cisplatin is one of the most encountered clinical problems resulting from post operation and gives rise to poor prognosis in patients diagnosed with gastric cancer (GC). Methods , this study aims to combine autophagy-related genes (ATGs) to provide an investigation of the susceptibility of victims with gastric malignancy to postoperative chemotherapy. Based on the TCGA database, gene expression data for GC patients undergoing and are using chemotherapy were integrated and analyzed. Prognostic genes were screened based on univariate and various analysis regression models. Subjects were divided into those with high and low-risk groups. This was analyzed by the utilization of the median risk score approach. The product limit estimator method had to be used to evaluate the OS and DFS. The accuracy of the prediction was resolved by the subject curve analysis. In addition, the carrying out of proper analysis was done in our work for some detailed assessments. The differential expression of ATGs is mainly related to chemotherapy resistance. Results, a total of 9 ATGs of chemotherapy administration outcomes in these suffers were screened. Based on GEO and TCGA databases, the model accurately predicted DFS and OS after chemotherapy administration. Conclusions, this study established prognostic markers based on 9 genes, which can predict ATGs related to chemotherapy susceptibility of GC patients, and provide better individualized treatment regimens for clinical practice.

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Section: Discussionsupporting

confidence: 93%

Prognostic Autophagy-Related Genes of Gastric Cancer Patients on Chemotherapy

Liu

et al. 2020

Preprint

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“…Both activating and inhibiting ER stress can overcome chemoresistance and radioresistance in cancer [70][71][72]. This indicates that the roles of ER stress in cell fate are multifaceted and context-dependent.…”

Section: Remodeling Of Er Stress Autophagy and Phagocytosismentioning

confidence: 99%

Functions and mechanisms of circular RNAs in cancer radiotherapy and chemotherapy resistance

et al. 2020

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Circular RNAs (circRNAs), one type of non-coding RNA, were initially misinterpreted as nonfunctional products of pre-mRNA mis-splicing. Currently, circRNAs have been proven to manipulate the functions of diverse molecules, including non-coding RNAs, mRNAs, DNAs and proteins, to regulate cell activities in physiology and pathology. Accumulating evidence indicates that circRNAs play critical roles in tumor genesis, development, and sensitivity to radiation and chemotherapy. Radiotherapy and chemotherapy are two primary types of intervention for most cancers, but their therapeutic efficacies are usually retarded by intrinsic and acquired resistance. Thus, it is urgent to develop new strategies to improve therapeutic responses. To achieve this, clarification of the underlying mechanisms affecting therapeutic responses in cancer is needed. This review summarizes recent progress and mechanisms of circRNAs in cancer resistance to radiation and chemotherapy, and it discusses the limitations of available knowledge and potential future directions.

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“…5c), suggesting that ER stress induction also regulates the PPARγ expression. To con rm the mechanism that ER stress induction kills bladder cancer cells, we then treated the cells with the ER stress inducer tunicamycin [41].…”

Section: Pparγ Activation Played a Pivotal Role In Killing Bladder Camentioning

confidence: 99%

Simvastatin-Romidepsin Combination Kills Bladder Cancer Cells Synergistically

Okubo

Miyai

Kato

et al. 2020

Preprint

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Abstract Background The HMG-CoA reductase inhibitor simvastatin activates AMP-activated protein kinase (AMPK) and thereby induces histone acetylation. We postulated that combining simvastatin with the histone deacetylase (HDAC) inhibitor romidepsin would kill bladder cancer cells by inducing histone acetylation cooperatively. Methods Bladder cancer cells (UMUC-3, T-24, J-82, MBT-2) were treated with simvastatin and romidepsin. Cell viability and clonogenicity were assessed by CCK-8 assay and colony formation assay. In-vivo efficacy was evaluated using murine subcutaneous tumor models. Flow cytometry was used to detect annexin-V positive cells and to evaluate cell cycle distribution and cellular reactive oxygen species (ROS) production. Induction of histone acetylation and the expression of AMPK, HDACs, peroxisome proliferator-activated receptor (PPAR) γ, cell-cycle regulators, and the endoplasmic reticulum (ER) stress markers were evaluated by western blotting. Results The combination of romidepsin and simvastatin induced robust apoptosis and killed bladder cancer cells synergistically (combination indexes < 1). It also suppressed colony formation significantly. In murine subcutaneous tumor models using MBT-2 cells, a 15-day treatment with 0.5 mg/kg romidepsin and 15 mg/kg simvastatin was well tolerated and inhibited tumor growth significantly. Mechanistically, the combination induced histone acetylation by activating AMPK. The combination also decreased the expression of HDACs, thus further promoting histone acetylation. This AMPK activation was essential for the combination’s action because compound C, an AMPK inhibitor, suppressed the combination-induced histone acetylation and the combination’s ability to induce apoptosis. We also found that the combination increased the expression of PPARγ, leading to ROS production. Furthermore, the combination induced ER stress and this ER stress was shown to be associated with increased AMPK expression and histone acetylation, thus playing an important role in the combination’s action. Our study also suggests there is a positive feedback cycle between ER stress induction and PPARγ expression. Conclusions The combination of simvastatin and romidepsin kills bladder cancer cells synergistically. Its mechanism of action includes ER stress induction, AMPK activation, histone acetylation, and increased PPARγ expression. Background There is currently no curative treatment for metastatic bladder cancer and development of novel treatment strategy is urgently needed. AMP-activated protein kinase (AMPK) is a cellular energy sensor, which is activated by impaired energy status such as glucose deprivation, ischemia, hypoxia, and oxidative stress, leading to inhibition of cellular growth to restore energy homeostasis [1]. Therefore, drugs activating AMPK have attracted much attention as novel anticancer agents [2–5]. HMG-CoA reductase inhibitors, which are widely used for treating dyslipidemia [6–9], are known to activate AMPK [10–12]. Simvastatin inhibits HMG-CoA reductase and has been shown to kill cancer cells in vitro [12–14], although its anticancer efficacy has not been proven yet in clinical trials [15].

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Tunicamycin specifically aggravates ER stress and overcomes chemoresistance in multidrug-resistant gastric cancer cells by inhibiting N-glycosylation

Cited by 140 publications

References 63 publications

Prognostic Autophagy-Related Genes of Gastric Cancer Patients on Chemotherapy

Prognostic Autophagy-Related Genes of Gastric Cancer Patients on Chemotherapy

Functions and mechanisms of circular RNAs in cancer radiotherapy and chemotherapy resistance

Simvastatin-Romidepsin Combination Kills Bladder Cancer Cells Synergistically

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