In-depth research of multidrug resistance related cell surface glycoproteome in gastric cancer

Li, Kai; Sun, Zhen; Zheng, Jie; Lu, Yuanyuan; Bian, Yangyang; Ye, Mingliang; Wang, Xin; Nie, Yongzhan; Zou, Hanfa; Fan, Daiming

doi:10.1016/j.jprot.2013.02.021

Cited by 26 publications

(21 citation statements)

References 49 publications

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“…Until now, only few studies have analyzed the surfaceome of chemoresistant cells [8, 9]. These studies have identified proteins that were overexpressed in MDR cells, such as CD44 [8], dihydropyridine receptor alpha 2 and laminin subunit alpha 5 [9].…”

Section: Introductionmentioning

confidence: 99%

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Carbonic anhydrase XII is a new therapeutic target to overcome chemoresistance in cancer cells

et al. 2015

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Multidrug resistance (MDR) in cancer cells is a challenging phenomenon often associated with P-glycoprotein (Pgp) surface expression. Finding new ways to bypass Pgp-mediated MDR still remains a daunting challenge towards the successful treatment of malignant neoplasms such as colorectal cancer.We applied the Cell Surface Capture technology to chemosensitive and chemoresistant human colon cancer to explore the cell surface proteome of Pgp-expressing cells in a discovery-driven fashion. Comparative quantitative analysis of identified cell surface glycoproteins revealed carbonic anhydrase type XII (CAXII) to be up-regulated on the surface of chemoresistant cells, similarly to Pgp. In cellular models showing an acquired MDR phenotype due to the selective pressure of chemotherapy, the progressive increase of the transcription factor hypoxia-inducible factor-1 alpha was paralleled by the simultaneous up-regulation of Pgp and CAXII. CAXII and Pgp physically interacted at the cell surface. CAXII silencing or pharmacological inhibition with acetazolamide decreased the ATPase activity of Pgp by altering the optimal pH at which Pgp operated and promoted chemosensitization to Pgp substrates in MDR cells.We propose CAXII as a new secondary marker of the MDR phenotype that influences Pgp activity directly and can be used as a pharmacological target for MDR research and potential treatment.

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Section: Introductionmentioning

confidence: 99%

“…These studies have identified proteins that were overexpressed in MDR cells, such as CD44 [8], dihydropyridine receptor alpha 2 and laminin subunit alpha 5 [9]. These cell surface proteins could be of clinical utility as potential biomarkers predictive of chemoresistance and/or potential therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Carbonic anhydrase XII is a new therapeutic target to overcome chemoresistance in cancer cells

et al. 2015

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“…ATP-binding cassette (ABC) transporters have been found to be involved in MDR. The most important ABC proteins are P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) (3,4), both of which are glycoproteins and can be affected by glycosylation in MDR (5).…”

Section: Introductionmentioning

confidence: 99%

Effect of brefeldin A and castanospermine on resistant cell lines as supplements in anticancer therapy

et al. 2016

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In the present study, we analyzed the influence of brefeldin A (BFA) and castanospermine (CAS) on the activity, stability and localization of P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) in various resistant cell lines. The impact of BFA and CAS on cell viability was assessed using the MTT test. Western blotting (WB) was performed to assess the effect of the inhibitors on the expression of the investigated proteins. Immunofluorescence was employed to assess the effect of BFA and CAS on the cellular localization of the proteins. Flow cytometry was used to verify the functional role of inhibitors on drug uptake and efflux. The MTT test showed that BFA had a significant effect on cell viability in LoVo/Dx and W1PR cell lines. WB analysis demonstrated that BFA partially blocked Pgp N-glycosylation and induced BCRP degradation and CASP 3-dependent apoptosis in W1TR cells; however, the BFA activity was p53-independent. CAS had no effect on the stability of Pgp but increased the level of non-glycosylated BCRP. The expression of p53 protein decreased in all of the cells that were treated with CAS. Immunofluorescence revealed that BFA caused a more granular Pgp signal in W1PR and BCRP in A2780T1 cells. Furthermore, BFA caused morphological changes in LoVo/Dx and W1TR cell lines. CAS also induced a granular signal in all of the cell lines, except W1TR. The flow cytometry showed higher dye accumulation in sensitive cell lines. We observed an increase in the mean fluorescence intensity (MFI) of Rho123 in LoVo/Dx cells treated with BFA and CAS, but no differences were observed in W1PR. BFA had no effect on the MFI of W1TR, but CAS led to an increase in the level of intracellular H33342 in W1TR and A2780T1 cells. These results suggest that these compounds are likely to be useful as supplements in anticancer therapy.

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“…Detection of MDR genes has been described using the methodology outlined in this article. For example, 56 cell membrane glycoproteins in leukemia samples could be successfully quantitated by antibody analysis of non-glycopeptides 83. Detection technology is constantly developing.…”

Section: Resultsmentioning

confidence: 99%

Detection approaches for multidrug resistance genes of leukemia

Chen

2017

DDDT

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Leukemia is a clonal malignant hematopoietic stem cell disease. It is the sixth most lethal cancer and accounts for 4% of all cancers. The main form of treatment for leukemia is chemotherapy. While some cancer types with a higher incidence than leukemia, such as lung and gastric cancer, have shown a sharp decline in mortality rates in recent years, leukemia has not followed this trend. Drug resistance is often regarded as the main clinical obstacle to effective chemotherapy in patients diagnosed with leukemia. Many resistance mechanisms have now been identified, and multidrug resistance (MDR) is considered the most important and prevalent mechanism involved in the failure of chemotherapy in leukemia. In order to reverse MDR and improve leukemia prognosis, effective detection methods are needed to identify drug resistance genes at initial diagnosis. This article provides a comprehensive overview of published approaches for the detection of MDR in leukemia. Identification of relevant MDR genes and methods for early detection of these genes will be needed in order to treat leukemia more effectively.

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In-depth research of multidrug resistance related cell surface glycoproteome in gastric cancer

Cited by 26 publications

References 49 publications

Carbonic anhydrase XII is a new therapeutic target to overcome chemoresistance in cancer cells

Carbonic anhydrase XII is a new therapeutic target to overcome chemoresistance in cancer cells

Effect of brefeldin A and castanospermine on resistant cell lines as supplements in anticancer therapy

Detection approaches for multidrug resistance genes of leukemia

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