Acquisition of doxorubicin resistance facilitates migrating and invasive potentials of gastric cancer MKN45 cells through up-regulating aldo–keto reductase 1B10

Morikawa, Yoshifumi; Kezuka, Chihiro; Endo, Shunsuke; Ikari, Akira; Soda, Midori; Yamamura, Ken‐ichi; Toyooka, Naoki; El‐Kabbani, Ossama; Hara, Akira; Matsunaga, Toshiyuki

doi:10.1016/j.cbi.2015.02.005

Cited by 42 publications

(40 citation statements)

References 50 publications

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“…Our recent publication on the upregulation of AKR1B10 in KE, where we hypothesised its ability to catalyse the reduction of carbonyls and xenobiotics may render keloid susceptible to chemotherapeutic resistance and thus explain some of the difficulties associated with management of KD to date [23, 151]. Both ALDH1A1 and the aforementioned upregulation of NOTCH4 in KE are also associated with drug resistance [152, 153].…”

Section: Resultsmentioning

confidence: 99%

Site-specific gene expression profiling as a novel strategy for unravelling keloid disease pathobiology

et al. 2017

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Keloid disease (KD) is a fibroproliferative cutaneous tumour characterised by heterogeneity, excess collagen deposition and aggressive local invasion. Lack of a validated animal model and resistance to a multitude of current therapies has resulted in unsatisfactory clinical outcomes of KD management. In order to address KD from a new perspective, we applied for the first time a site-specific in situ microdissection and gene expression profiling approach, through combined laser capture microdissection and transcriptomic array. The aim here was to analyse the utility of this approach compared with established methods of investigation, including whole tissue biopsy and monolayer cell culture techniques. This study was designed to approach KD from a hypothesis-free and compartment-specific angle, using state-of-the-art microdissection and gene expression profiling technology. We sought to characterise expression differences between specific keloid lesional sites and elucidate potential contributions of significantly dysregulated genes to mechanisms underlying keloid pathobiology, thus informing future explorative research into KD. Here, we highlight the advantages of our in situ microdissection strategy in generating expression data with improved sensitivity and accuracy over traditional methods. This methodological approach supports an active role for the epidermis in the pathogenesis of KD through identification of genes and upstream regulators implicated in epithelial-mesenchymal transition, inflammation and immune modulation. We describe dermal expression patterns crucial to collagen deposition that are associated with TGFβ-mediated signalling, which have not previously been examined in KD. Additionally, this study supports the previously proposed presence of a cancer-like stem cell population in KD and explores the possible contribution of gene dysregulation to the resistance of KD to conventional therapy. Through this innovative in situ microdissection gene profiling approach, we provide better-defined gene signatures of distinct KD regions, thereby addressing KD heterogeneity, facilitating differential diagnosis with other cutaneous fibroses via transcriptional fingerprinting, and highlighting key areas for future KD research.

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Section: Resultsmentioning

confidence: 99%

Site-specific gene expression profiling as a novel strategy for unravelling keloid disease pathobiology

et al. 2017

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“…Morikawa et al . also verified that acquisition of doxorubicin resistance facilitates migrating and invasive potentials of gastric cancer. Fortunately, a former research has manifested the function of RES on the reversion of DOX resistance by inhibiting epithelial–mesenchymal transition through modulating PTEN/Akt signaling pathway in gastric cancer .…”

Section: Introductionmentioning

confidence: 57%

Effect of resveratrol on doxorubicin resistance in breast neoplasm cells by modulating PI3K/Akt signaling pathway

2018

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In the study, we probed into the effect of Resveratrol (RES) on Doxorubicin (DOX)-resistant breast neoplasm cell line MCF-7/DOX as well as the mechanism of RES underlying the DOX-resistant breast cancer. CCK-8 assay was utilized to assess the survival rates and sensitivity of breast neoplasm cell lines MCF-7 or MDA-MB-231 to DOX and RES. DOX-resistant MCF-7 cell line was successfully cultivated with DOX dose increasing and was named MCF-7/DOX. Afterwards, wound healing and Transwell assays were performed to measure the migration and invasion capabilities of MCF-7/DOX cells, while cell propagation and apoptosis were determined by colony formation assay and flow cytometry analysis. Both western blotting and immunohistochemistry were conducted to examine the expression of proteins involved in PI3K/Akt signaling pathway. Nude mice xenograft model was constructed to further verify the effects of DOX and RES on breast neoplasm in vivo. RES restored DOX sensitivity in MCF-7/DOX cells, inhibiting biological functions of MCF-7/DOX cells and promoting cell apoptosis in vitro and impeding tumor growth in vivo. It was revealed by the mechanistic studies that MCF-7/DOX cells could regain the drug sensibility with RES treatment through inactivating the PI3K/Akt signal transduction pathway. RES could reverse DOX resistance in breast neoplasm cells and inhibited DOX-resistant breast cancer cell propagation and metastasis and facilitated cell apoptosis by modulating PI3K/Akt signaling pathway. © 2018 IUBMB Life, 70(6):491-500, 2018.

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“…A study has shown that overexpression of AKR1B10 results in low levels of retinoic acid, which could lead to dedifferentiation of cells and tumor development . Overexpression of AKR1B10 has also been found to confer resistance to several anti‐cancer drugs, including cisplatin and doxorubicin . Since cisplatin is the major and first‐line reagent used in chemotherapy of head and neck cancer, high expression of AKR1B10 may compromise its effectiveness and lead to tumor recurrence.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of AKR1B10 predicts tumor recurrence and short survival in oral squamous cell carcinoma patients

Fang

Lin

Chen

2019

J Oral Pathology Medicine

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Background Aldo‐keto reductase family 1 member B10 (AKR1B10) is an enzyme implicated in physiological xenobiotic detoxification and also in pathological carcinogenesis. Overexpression of AKR1B10 has been reported in oral squamous cell carcinoma (OSCC), but its correlation with clinical prognosis is controversial. The aim of this study was to investigate and clarify the role of AKR1B10 in OSCC carcinogenesis. Methods Tumor tissue specimens were surgically obtained from 107 patients with OSCC. The expression of AKR1B10 was analyzed by immunohistochemistry to explore the relationship between the level of AKR1B10 and clinicopathological features of OSCC patients. Kaplan‐Meier survival and Cox proportional hazard analysis were used to determine the prognostic value of AKR1B10 in OSCC. Results High expression of AKR1B10 was found to be associated with tumor size (P = 0.043), perineural invasion (P = 0.012), and recurrence (P = 0.001) in OSCC. Cox model analysis revealed that high expression of AKR1B10 is significantly associated with poor overall and disease‐free survival in OSCC patients. With the combination of clinicopathological factors in analysis, we found that the expression level of AKR1B10 was a practical indicator that could categorize OSCC patients into different risk groups. High expression of AKR1B10 was associated with a reduced survival in patients with well and moderately differentiated OSCC and even a high incidence of tumor recurrence in the patients with late‐stage (III and IV) disease. Conclusion We validated and expanded data on the expression of AKR1B10 in OSCC, suggesting that it is a valuable biomarker for prognostic prediction of recurrence and survival in OSCC.

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Acquisition of doxorubicin resistance facilitates migrating and invasive potentials of gastric cancer MKN45 cells through up-regulating aldo–keto reductase 1B10

Cited by 42 publications

References 50 publications

Site-specific gene expression profiling as a novel strategy for unravelling keloid disease pathobiology

Site-specific gene expression profiling as a novel strategy for unravelling keloid disease pathobiology

Effect of resveratrol on doxorubicin resistance in breast neoplasm cells by modulating PI3K/Akt signaling pathway

Overexpression of AKR1B10 predicts tumor recurrence and short survival in oral squamous cell carcinoma patients

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