Proton pump inhibitor pantoprazole abrogates adriamycin-resistant gastric cancer cell invasiveness via suppression of Akt/GSK-β/β-catenin signaling and epithelial–mesenchymal transition

Zhang, Bin; Yang, Yan; Shi, Xiaoting; Liao, Wan-Yu; Chen, Min; Cheng, Alfred Sze‐Lok; Yan, Hongli; Fang, Cheng; Zhang, Shu; Xu, Guifang; Shen, Shanshan; Huang, Shenglan; Chen, Guangxia; Lv, Ying; Ling, Tao; Zhang, Xiaoqi; Wang, Lei; Zhuge, Yuzheng; Zou, Xiaoping

doi:10.1016/j.canlet.2014.10.016

Cited by 70 publications

(52 citation statements)

References 36 publications

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“…A previous study showed that FILIP1L inhibited cancer cell invasion and metastasis by blocking WNT/β-catenin signaling pathway activity [16]. GSK-3β, which mediates Akt signaling and prevents β-catenin phosphorylation and degradation, is aberrantly activated in many types of cancer [28, 29]. In addition, Akt/GSK-3β/β-catenin signaling pathway activity promotes cell motility, cell survival, angiogenesis, and carcinogenesis in colorectal cancer [30, 31].…”

Section: Discussionmentioning

confidence: 99%

Filamin A interacting protein 1-like expression inhibits progression in colorectal cancer

Park

Lee

et al. 2016

Oncotarget

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Filamin A interacting protein 1-like (FILIP1L) expression, which is decreased in various cancers, may inhibit carcinogenesis. In this study, we evaluated the effects of FILIP1L on oncogenic behavior and prognosis in colorectal cancer. siRNA-mediated FILIP1L knockdown enhanced tumor cell migration and invasion and inhibited apoptosis and cell cycle arrest in COLO205 cells. pcDNA-myc vector-mediated FILIP1L overexpression suppressed tumor cell migration and invasion and induced apoptosis and cell cycle arrest in HCT116 cells. FILIP1L knockdown enhanced angiogenesis by increasing VEGF-A and HIF-1α levels and decreasing angiostatin level. FILIP1L overexpression suppressed angiogenesis by decreasing VEGF-A and -D l level and increasing angiostatin and endostatin levels. Phosphorylated β-catenin levels decreased and phosphorylated Akt and GSK-3β levels increased following FILIP1L knockdown. FILIP1L overexpression had the opposite effects. FILIP1L expression was associated with reductions in tumor size, cell differentiation, lymphovascular invasion, stage, invasion depth and lymph node metastasis, and with longer overall survival. Mean Ki-67 labeling indexes and microvessel density values were lower in FILIP1L-positive tumors than in FILIP1L-negative tumors. These results indicate that FILIP1L suppresses tumor progression by inhibiting cell proliferation and angiogenesis in colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

Filamin A interacting protein 1-like expression inhibits progression in colorectal cancer

Park

Lee

et al. 2016

Oncotarget

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“…37 In brief, ~1 × 10 3 cells/well were seeded into six-well plates overnight and then incubated with indicated concentrations of Cu-I. After 14 days, the colonies were fixed with methanol and stained with crystal violet.…”

Section: Methodsmentioning

confidence: 99%

“…37 Cells were plated to 24-well plates 24 h prior to transfection experiments. Transfection experiment was carried out by adding 380 ng of reporter plasmid along with a pRL-TK reporter plasmid (20 ng) as a control for transfection efficiency.…”

Section: Methodsmentioning

confidence: 99%

Low nanomolar concentrations of Cucurbitacin-I induces G2/M phase arrest and apoptosis by perturbing redox homeostasis in gastric cancer cells in vitro and in vivo

Deng

Zhang

et al. 2016

Cell Death Dis

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Cucurbitacin-I (Cu-I, also known as Elatericin B or JSI-124) is developed to inhibit constitutive and abnormal activation of STAT3 in many cancers, demonstrating a potent anticancer activity by targeting disruption of STAT3 function. Here, we for the first time systematically studied the underlying molecular mechanisms of Cu-I-induced gastric cancer cell death both in vitro and in vivo. In our study, we show that Cu-I markedly inhibits gastric cancer cell growth by inducing G2/M phase cell cycle arrest and apoptosis at low nanomolar concentrations via a STAT3-independent mechanism. Notably, Cu-I significantly decreases intracellular GSH/GSSG ratio by inhibiting NRF2 pathway to break cellular redox homeostasis, and subsequently induces the expression of GADD45α in a p53-independent manner, and activates JNK/p38 MAPK signaling. Interestingly, Cu-I-induced GADD45α and JNK/p38 MAPK signaling form a positive feedback loop and can be reciprocally regulated by each other. Therefore, the present study provides new insights into the mechanisms of antitumor effects of Cu-I, supporting Cu-I as an attractive therapeutic drug in gastric cancer by modulating the redox balance.

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“…This study demonstrated that adenoviral expression of Dkk-1 was efficient in modulating activation of Wnt signaling and also proved that CSC-targeting gene therapy could be effective in gastric cancer. Recently, Zhang et al [256] reported that the proton pump inhibitor pantoprazole treatment inhibited the hyper-activated Wnt/b-catenin signaling and reduced cell invasiveness of chemotherapy-resistant gastric cancer cells and epithelial-mesenchymal transition. This work, besides giving evidence that the enhanced aggressive phenotype appeared to be mediated by activation of the canonical Wnt/b-catenin signaling pathway, it also showed that it is possible to reduce the aggressiveness of gastric cancer with a proton pump inhibitor [256] .…”

Section: Targeting the Wnt/b-catenin Pathway As Potential Therapy In mentioning

confidence: 99%

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

Chiurillo

2015

WJEM

270

219

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Gastric cancer remains one of the most common cancers worldwide and one of the leading cause for cancerrelated deaths. Gastric adenocarcinoma is a multifactorial disease that is genetically, cytologically and architecturally more heterogeneous than other gastrointestinal carcinomas. The identification of specific membrane, intracellular, and extracellular components of the Wnt pathway has revealed potential targets for gastric cancer therapy. High-throughput "omics" approaches will help in the search for Wnt pathway antagonist in the near future.

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Proton pump inhibitor pantoprazole abrogates adriamycin-resistant gastric cancer cell invasiveness via suppression of Akt/GSK-β/β-catenin signaling and epithelial–mesenchymal transition

Cited by 70 publications

References 36 publications

Filamin A interacting protein 1-like expression inhibits progression in colorectal cancer

Filamin A interacting protein 1-like expression inhibits progression in colorectal cancer

Low nanomolar concentrations of Cucurbitacin-I induces G2/M phase arrest and apoptosis by perturbing redox homeostasis in gastric cancer cells in vitro and in vivo

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

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