Gene expression profiling for analysis acquired oxaliplatin resistant factors in human gastric carcinoma TSGH-S3 cells: The role of IL-6 signaling and Nrf2/AKR1C axis identification

Chen, Chih‐Cheng; Chu, Chia Bao; Liu, Ko Jiunn; Huang, Chi Ying F.; Chang, Jang Yang; Pan, Wen; Chen, Huang Hui; Cheng, Yun Hsia; Lee, Kuan Der; Chen, Miao Fen; Kuo, Ching Chuan; Chen, Li Tzong

doi:10.1016/j.bcp.2013.07.025

Cited by 49 publications

(47 citation statements)

References 51 publications

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“…AKR1C1 is reported to be overexpressed in cisplatin‐resistant cancer cell lines 14,16 and up‐regulated in metastatic lesions of human bladder cancer 17 . Overexpressed AKR1C1 positively correlates to cisplatin resistance in HNSCC cells, 16 bladder cancer cells 17 and colon cancer cells 14 . In this study, we found AKR1C1 contributing to cisplatin resistance in NPC in vitro.…”

Section: Discussionsupporting

confidence: 59%

Loss of AKR1C1 is a good prognostic factor in advanced NPC cases and increases chemosensitivity to cisplatin in NPC cells

Zhou

Shen

Yang

et al. 2020

J Cellular Molecular Medi

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Cisplatin resistance is one of the main obstacles in the treatment of advanced nasopharyngeal carcinoma (NPC). AKR1C1 is a member of the Aldo‐keto reductase superfamily (AKRs), which converts aldehydes and ketones to their corresponding alcohols and has been reported to be involved in chemotherapeutic resistance of multiple drugs. The expression and function of AKR1C1 in NPC have not been reported until now. The aim of this research was to investigate the expression of AKR1C1 and it is role in cisplatin resistance in NPC. AKR1C1 protein expression was detected by immunohistochemistry in human NPC tissues and by Western blot assays in NPC and immortalized nasopharyngeal epithelial cells. The effects of AKR1C1 knock‐down by siRNA on proliferation, migration and invasion in NPC cells were evaluated by CCK8, wound healing and transwell assays. To evaluate the effects of AKR1C1 silencing on cisplatin sensitivity in NPC cells, CCK8 assays were used to detect cell proliferation, flow cytometry was used to detect cell cycle distribution, and flow cytometry and DAPI staining were used to detect cell apoptosis. AKR1C1 down‐regulation was associated with advanced clinicopathological characters such as larger tumor size, more lymphatic nodes involvement, with metastasis and later clinical stages, while AKR1C1 down‐regulation was a good prognostic factor for overall survival (OS) in NPC patients. In vitro study showed that AKR1C1 was not directly involved in the malignant biological behaviours such as proliferation, cell cycle progression and migration of NPC cells, whereas AKR1C1 knock‐down could enhance cisplatin sensitivity of NPC cells. These results suggest that AKR1C1 is a potential marker for predicting cisplatin response and could serve as a molecular target to increase cisplatin sensitivity in NPC.

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Section: Discussionsupporting

confidence: 59%

Loss of AKR1C1 is a good prognostic factor in advanced NPC cases and increases chemosensitivity to cisplatin in NPC cells

Zhou

Shen

Yang

et al. 2020

J Cellular Molecular Medi

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“…Finally, Nrf2 activation can contribute to drug-resistance in digestive tract cancers. AKR1C was reported to be elevated in an oxaliplatinresistant human gastric carcinoma cell line, and knockout of Nrf2 can decrease AKR1C expression and reverse drug-resistance to oxaliplatin in S3 cells (Chen et al, 2013). Moreover, we found that oxaliplatin activate the Nrf2 signaling pathway in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 55%

Luteolin Sensitizes Two Oxaliplatin-Resistant Colorectal Cancer Cell Lines to Chemotherapeutic Drugs Via Inhibition of the Nrf2 Pathway

Chian

Li²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Oxaliplatin is a first-line therapy for colorectal cancer, but cancer cell resistance to the drug compromises its efficacy. To explore mechanisms of drug resistance, we treated colorectal cancer cells (HCT116 and SW620) long-term with oxaliplatin and established stable oxaliplatin-resistant lines (HCT116-OX and SW620-OX). Compared with parental cell lines, IC 50 s for various chemotherapeutic agents (oxaliplatin, cisplatin and doxorubicin) were increased in oxaliplatin-resistant cell lines and this was accompanied by activation of nuclear factor erythroid-2 p45-related factor 2 (Nrf2) and NADPH quinone oxidoreductase 1 (NQO1) . Furthermore, luteolin inhibited the Nrf2 pathway in oxaliplatin-resistant cell lines in a dose-dependent manner. Luteolin also inhibited Nrf2 target gene [NQO1, heme oxygenase-1 (HO-1) and GSTα1/2] expression and decreased reduced glutathione in wild type mouse small intestinal cells. There was no apparent effect in Nrf2-/-mice. Luteolin combined with other chemotherapeutics had greater anti-cancer activity in resistant cell lines (combined index values below 1), indicating a synergistic effect. Therefore, adaptive activation of Nrf2 may contribute to the development of acquired drug-resistance and luteolin could restore sensitivity of oxaliplatin-resistant cell lines to chemotherapeutic drugs. Inhibition of the Nrf2 pathway may be the mechanism for this restored therapeutic response.

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“…A clear association has been reported between gastric cancer and chronic inflammation (1-3). Pro-inflammatory factors, including interleukin-1 (IL-1), IL-6 and tumor necrosis factor (TNF), may not only play roles in inflammation-associated carcinogenesis (4), but may also influence the chemotherapeutic sensitivity during gastric cancer treatment (5,6). IL-33 (previously known as NF-HEV), an 18-kDa protein, is a new member of the IL-1 family (7).…”

Section: Introductionmentioning

confidence: 99%

IL-33-induced JNK pathway activation confers gastric cancer chemotherapy resistance

Ye¹,

Zhao²,

Weng³

et al. 2015

Oncology Reports

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Abstract. Inflammation is regarded as one of the major hallmarks of tumors, and has a very close relationship with gastric cancer. Interleukin-33 (IL-33), a new member of the IL-1 family, plays an important role in both inflammatory disease and tumors. The present study was designed to explore the effects of IL-33 on the proliferation, drug sensitivity, and the invasiveness of gastric cancer cells in vitro. IL-33 at concentrations lower than 100 pg/ml did not alter the inhibitory rate of gastric cancer cells. Moreover, IL-33 at these low concentrations protected against platinum-induced apoptosis in various gastric cancer cell lines, yet not in normal gastric epithelial cells. We also found that IL-33 increased the activation of the JNK pathway, and enhanced the expression of ST2. Furthermore, SP600125, a selective inhibitor of the JNK pathway, significantly blocked the protective effects of IL-33 in gastric cancer cells. In addition, Matrigel invasion assay showed that IL-33 markedly promoted gastric cancer cell invasion. In conclusion, the present study demonstrated that IL-33 protected against platinum-induced apoptosis and promoted cell invasion via activation of the JNK pathway in gastric cancer cells. In light of the prevalence of platinumbased chemotherapeutics in the treatment of gastric cancer, our results suggest that the level of IL-33 should be monitored during the treatment of gastric cancer, particularly when using platinum-based chemotherapeutics. IntroductionGastric cancer is one of the most common types of cancers. Over 1.6 million individuals succumb to gastric cancer each year in China. The Chinese incidence of gastric cancer accounts for more than 40% of the worldwide occurrences. Moreover, the progression-free survival and overall survival rates of gastric cancer patients in China are much lower than those in Europe and the US. Therefore, research concerning the characteristics and pathogenesis of gastric cancer in Chinese patients is urgently needed.Gastric cancer can be influenced by a wide range of genetic and environmental factors. A clear association has been reported between gastric cancer and chronic inflammation (1-3). Pro-inflammatory factors, including interleukin-1 (IL-1), IL-6 and tumor necrosis factor (TNF), may not only play roles in inflammation-associated carcinogenesis (4), but may also influence the chemotherapeutic sensitivity during gastric cancer treatment (5,6). IL-33 (previously known as NF-HEV), an 18-kDa protein, is a new member of the IL-1 family (7). Traditionally, the IL-1 family is well known for their effects on host defense, immune regulation and inflammation (7). However, recent research suggests that the IL-1 family is also involved in cancer development. For example IL-18, another member of the IL-1 family, acts as a pleiotropic cytokine in many types of cancer cells, and influences the invasion of gastric cancer cells under hypoxia (8). A high level of IL-18 in serum has been intensively associated with a wide variety of tumors, such as hepatocellular (9) a...

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Gene expression profiling for analysis acquired oxaliplatin resistant factors in human gastric carcinoma TSGH-S3 cells: The role of IL-6 signaling and Nrf2/AKR1C axis identification

Cited by 49 publications

References 51 publications

Loss of AKR1C1 is a good prognostic factor in advanced NPC cases and increases chemosensitivity to cisplatin in NPC cells

Loss of AKR1C1 is a good prognostic factor in advanced NPC cases and increases chemosensitivity to cisplatin in NPC cells

Luteolin Sensitizes Two Oxaliplatin-Resistant Colorectal Cancer Cell Lines to Chemotherapeutic Drugs Via Inhibition of the Nrf2 Pathway

IL-33-induced JNK pathway activation confers gastric cancer chemotherapy resistance

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