Rofecoxib augments anticancer effects by reversing intrinsic multidrug resistance gene expression in BGC-823 gastric cancer cells

2010 ◽  
Vol 11 (1) ◽  
pp. 34-42 ◽  
Author(s):  
Feng Shang ZHU ◽  
Xi Mei CHEN ◽  
Zhi Gang HUANG ◽  
Zhi Rong WANG ◽  
Dong Wei ZHANG ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Resistance Gene ◽  
Gastric Cancer Cells ◽  
Multidrug Resistance Gene ◽  
Anticancer Effects

ZNRD1 mediates resistance of gastric cancer cells to methotrexate by regulation of IMPDH2 and Bcl-2

2006 ◽  
Vol 84 (2) ◽  
pp. 199-206 ◽  
Author(s):  
Liu Hong ◽  
Taidong Qiao ◽  
Yu Han ◽  
Shuang Han ◽  
Xiaoyin Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Human Cancer ◽  
Sensitivity Analyses ◽  
Nucleic Acid Binding ◽  
Inosine Monophosphate Dehydrogenase ◽  
Gastric Cancer Cells ◽  
Multidrug Resistance Gene

We previously showed that downregulation of a transcription-associated gene (ZNRD1) could reverse the resistant phenotype of gastric cancer cells through regulation of the transcription of multidrug resistance gene 1 (MDR1). In the present study, we determined both known and novel differentially expressed genes in VCR-induced multidrug resistant gastric cancer cell SGC7901/VCR transfected with ZNRD1 siRNA or empty vector control. Screening was performed using the Human Cancer Xpro(tm) HC-III plus arrays, containing 3072 cancer-related cDNAs. Ten genes, involved in cell cycle control, nucleic acid binding, and protein phosphorylation, among other functions, underwent more than 5-fold change. Of the downregulated genes we chose Inosine monophosphate dehydrogenase 2 (IMPDH2) for further validation by quantitative RT-PCR. In vitro and in vivo drug sensitivity analyses revealed that inhibition of ZNRD1 and IMPDH2 activity sensitized SGC7901/VCR cells to methotrexate. Additionally, inhibition of ZNRD1 could suppress adriamycin-induced apoptosis and significantly downregulate the expression of Bcl-2, but it did not alter the expression of the glutathione-S-transferase, or intracellular glutathione content. Taken together, the findings suggest that ZNRD1 could act as a modulator of methotrexate chemotherapy in gastric cancer cells through the regulation of IMPDH2 and Bcl-2.Key words: ZNRD1, IMPDH2, multidrug resistance, apoptosis, gastric cancer.

scholarly journals Restoration of klotho gene expression induces apoptosis and autophagy in gastric cancer cells: tumor suppressive role of klotho in gastric cancer

2013 ◽  
Vol 13 (1) ◽  
pp. 18 ◽  
Author(s):  
Biao Xie ◽  
Jianping Zhou ◽  
Guoshun Shu ◽  
Dong-cai Liu ◽  
Jiapeng Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Cancer Cells ◽  
Gastric Cancer Cells ◽  
Klotho Gene

scholarly journals Oral absorption and pharmacokinetics of Methadone HCl and intestinal multidrug resistance gene expression in horses

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Renata Lehn Linardi ◽  
Steven A Barker ◽  
Charles Short ◽  
Konstantin G Kousoulas ◽  
Li‐Ju Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multidrug Resistance ◽  
Resistance Gene ◽  
Oral Absorption ◽  
Multidrug Resistance Gene

scholarly journals The effects of dietary curcumin and rutin on colonic inflammation and gene expression in multidrug resistance gene-deficient (mdr1a−/−) mice, a model of inflammatory bowel diseases

2008 ◽  
Vol 101 (2) ◽  
pp. 169-181 ◽  
Author(s):  
Katia Nones ◽  
Yvonne E. M. Dommels ◽  
Sheridan Martell ◽  
Christine Butts ◽  
Warren C. McNabb ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multidrug Resistance ◽  
Resistance Gene ◽  
Inflammatory Bowel Diseases ◽  
Pregnane X Receptor ◽  
Multidrug Resistance Gene ◽  
Colonic Inflammation ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Pathway Analyses

Damage of the intestinal epithelial barrier by xenobiotics or reactive oxygen species and a dysregulated immune response are both factors involved in the pathogenesis of inflammatory bowel diseases (IBD). Curcumin and rutin are polyphenolic compounds known to have antioxidant and anti-inflammatory activities, but their mechanism(s) of action are yet to be fully elucidated. Multidrug resistance gene-deficient (mdr1a− / − ) mice spontaneously develop intestinal inflammation, predominantly in the colon, with pathology similar to IBD, so this mouse model is relevant for studying diet–gene interactions and potential effects of foods on remission or development of IBD. The present study tested whether the addition of curcumin or rutin to the diet would alleviate colonic inflammation in mdr1a− / −  mice. Using whole-genome microarrays, the effect of dietary curcumin on gene expression in colon tissue was also investigated. Twelve mice were randomly assigned to each of three diets (control (AIN-76A), control +0·2 % curcumin or control +0·1 % rutin) and monitored from the age of 7 to 24 weeks. Curcumin, but not rutin, significantly reduced histological signs of colonic inflammation in mdr1a− / −  mice. Microarray and pathway analyses suggested that the effect of dietary curcumin on colon inflammation could be via an up-regulation of xenobiotic metabolism and a down-regulation of pro-inflammatory pathways, probably mediated by pregnane X receptor (Pxr) and peroxisome proliferator-activated receptor α (Ppara) activation of retinoid X receptor (Rxr). These results indicate the potential of global gene expression and pathway analyses to study and better understand the effect of foods in modulating colonic inflammation.

scholarly journals Berberine Improves Chemo-Sensitivity to Cisplatin by Enhancing Cell Apoptosis and Repressing PI3K/AKT/mTOR Signaling Pathway in Gastric Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Yingying Kou ◽  
Bending Tong ◽  
Weiqing Wu ◽  
Xiangqing Liao ◽  
Min Zhao
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Mtor Signaling ◽  
Multi Drug Resistance ◽  
Gastric Cancer Cells

Gastric cancer is one of the most common malignancies ranks as the second leading cause of cancer-related mortality in the world. Cisplatin (DDP) is commonly used for gastric cancer treatment, whereas recurrence and metastasis are common because of intrinsic and acquired DDP-resistance. The aim of this study is to examine the effects of berberine on the DDP-resistance in gastric cancer and explore the underling mechanisms. In this study, we established the DDP-resistant gastric cancer cells, where the IC50 values of DDP in the BGC-823/DDP and SGC-7901/DDP were significantly higher than that in the corresponding parental cells. Berberine could concentration-dependently inhibited the cell viability of BGC-823 and SGC-7901 cells; while the inhibitory effects of berberine on the cell viability were largely attenuated in the DDP-resistant cells. Berberine pre-treatment significantly sensitized BGC-823/DDP and SGC-7901/DDP cells to DDP. Furthermore, berberine treatment concentration-dependently down-regulated the multidrug resistance-associated protein 1 and multi-drug resistance-1 protein levels in the BGC-823/DDP and SGC7901/DDP cells. Interestingly, the cell apoptosis of BGC-823/DDP and SGC-7901/DDP cells was significantly enhanced by co-treatment with berberine and DDP. The results from animals also showed that berberine treatment sensitized SGC-7901/DDP cells to DDP in vivo. Mechanistically, berberine significantly suppressed the PI3K/AKT/mTOR in the BGC-823/DDP and SGC-7901/DDP cells treated with DDP. In conclusion, we observed that berberine sensitizes gastric cancer cells to DDP. Further mechanistic findings suggested that berberine-mediated DDP-sensitivity may be associated with reduced expression of drug transporters (multi-drug resistance-1 and multidrug resistance-associated protein 1), enhanced apoptosis and repressed PI3K/AKT/mTOR signaling.

DJ-1 is involved in the multidrug resistance of SGC7901 gastric cancer cells through PTEN/PI3K/Akt/Nrf2 pathway

2020 ◽  
Vol 52 (11) ◽  
pp. 1202-1214
Author(s):  
Lejia Qiu ◽  
Zhaoxia Ma ◽  
Xiaoran Li ◽  
Yizhang Deng ◽  
Guangling Duan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Gastric Cancer Cells ◽  
Glycoprotein P ◽  
Nrf2 Pathway ◽  
P Glycoprotein ◽  
New Findings ◽  
Nrf2 Signaling Pathway ◽  
Common Malignancy

Abstract Gastric cancer is a common malignancy worldwide. The occurrence of multidrug resistance (MDR) is the major obstacle for effective gastric cancer chemotherapy. In this study, the in-depth molecular mechanism of the DJ-1-induced MDR in SGC7901 gastric cancer cells was investigated. The results showed that DJ-1 expression level was higher in MDR variant SGC7901/VCR cells than that in its parental SGC7901 cells. Moreover, DJ-1 overexpression conferred the MDR phenotype to SGC7901 cells, while DJ-1 knockdown in SGC7901/VCR cells induced re-sensitization to adriamycin, vincristine, cisplatin, and 5-fluorouracil. These results suggested that DJ-1 mediated the development of MDR in SGC7901 gastric cancer cells. Importantly, further data revealed that the activation of PI3k/Akt and Nrf2 signaling pathway were required for the DJ-1-induced MDR phenotype in SGC7901 gastric cancer cells. Meanwhile, we found that PI3k/Akt pathway was activated probably through DJ-1 directly binding to and negatively regulating PTEN, consequently resulting in Nrf2 phosphorylation and activation, and thereby inducing Nrf2-dependent P-glycoprotein (P-gp) and Bcl-2 expressions in the DJ-1-mediated MDR of SGC7901 gastric cancer cells. Overall, these results revealed that activating PTEN/PI3K/Akt/Nrf2 pathway and subsequently upregulating P-gp and Bcl-2 expression could be a critical mechanism by which DJ-1 mediates the development of MDR in SGC7901 gastric cancer cells. The new findings may be helpful for understanding the mechanisms of MDR in gastric cancer cells, prompting its further investigation as a molecular target to overcome MDR.

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