Mitochondrial comparative proteomics of human ovarian cancer cells and their platinum‐resistant sublines

Dai, Zhiqin; Yin, Jie; He, Haojie; Li, Wenrui; Hou, Chunmei; Qian, Xiaohong; Mao, Ning; Pan, Lingya

doi:10.1002/pmic.200900685

Cited by 55 publications

(32 citation statements)

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“…Furthermore, short hairpin RNA (shRNA)-mediated loss in functional PRDX3 expression led to significant suppression of migration and transendothelial invasion in MCF-7 breast cancer cells in vitro and significant inhibition of breast cancer metastasis in vivo (Kim et al, 2009;Li et al, 2009;Liu et al, 2010;Wu et al, 2010). Recently, abundant evidence has also confirmed that tissue-specific expression of PRDX3 plays an important role in hepatocarcinoma progression (Dai et al, 2010). Qiao et al has analyzed the comparative proteomic profiles between HCC tumors and adjacent non-tumor tissues by 2-DE and MALDI-TOF MS, and identified differentially expressed molecules which may help to develop effective therapeutic strategies against HCC.…”

Section: Discussionmentioning

confidence: 99%

Serum Peroxiredoxin3 is a Useful Biomarker for Early Diagnosis and Assessemnt of Prognosis of Hepatocellular Carcinoma in Chinese Patients

Shi¹,

Wu²,

Yang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Recently, peroxiredoxin3 (PRDX3) was identified as a novel molecular marker for the progression of hepatocellular carcinoma (HCC). However, its potential clinical application as a serum marker for the early diagnosis and prognosis of HCC has not been investigated. Methods: PRDX3, alpha-fetaprotein (AFP), and other biochemical parameters were measured in serum samples from 297 Chinese patients, including 96 with HCC, 98 with liver cirrhosis (LC), and 103 healthy controls (HCs). Correlations between serum PRDX3 expression and clinicopathological variables and the relationship between serum PRDX3 expression and prognosis were analyzed. Results: Serum PRDX3 was significantly higher in HCC patients than in the LC and HC groups. The sensitivity and specificity of serum PRDX3 for the diagnosis of HCC were 85.9% and 75.3%, respectively, at a cutoff of 153.26 ng/mL, and the area under the curve was 0.865. Moreover, serum PRDX3 expression was strongly associated with AFP level, tumor diameter, TNM stage, and portal vein invasion. Kaplan-Meier curve analysis revealed that HCC patients with high serum PRDX3 expression had a shorter median survival time than those with low PRDX3 expression. Moreover, serum PRDX3 expression was an independent risk factor for overall survival. The inverse correlation between serum PRDX3 and patient survival remained significant in patients with early-stage HCC and in those with normal serum AFP levels. Conclusions: Serum PRDX3 can be used as a noninvasive biomarker for the diagnosis and/or prognosis of HCC.

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Section: Discussionmentioning

confidence: 99%

Serum Peroxiredoxin3 is a Useful Biomarker for Early Diagnosis and Assessemnt of Prognosis of Hepatocellular Carcinoma in Chinese Patients

Shi¹,

Wu²,

Yang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Classical antioxidant genes related to cancer are the superoxide dismutase (SOD), catalase, GST, glutathione peroxidase, peroxiredoxins and thioredoxin (Trx) (12)(13)(14)(15) (19). PRDX3 has been shown to be overexpressed in mesothelioma, hepatocellular carcinoma, breast cancer and ovarian cancer (20)(21)(22)(23), which suggest that PRDX3 may be involved in tumorigenesis and progression.…”

Section: Introductionmentioning

confidence: 99%

Detection and identification of peroxiredoxin 3 as a biomarker in hepatocellular carcinoma by a proteomic approach

et al. 2012

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Abstract. Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis due to resistance to conventional chemotherapy and limited efficacy of radiotherapy. Thus, alternative therapeutic strategies need to be established. In order to search for a useful biomarker to improve its efficacy, we conducted a two-dimensional gel electrophoresis and MALDI-TOF MS-based comparative proteomic analysis to profile the differentially expressed proteins between HCC tumor tissues with histological evidence and the adjacent non-tumor tissues. Twenty-two out of 43 dysregulated proteins were identified, including 15 upregulated proteins, and 7 downregulated proteins (over 2-fold, P<0.01). The expression of peroxiredoxin 3 (PRDX3) at the mRNA and protein levels was confirmed by RT-PCR and western blotting in HCC cell lines, and HCC samples, and further analysed by immunohistochemistry in HCC samples of different clinical pathological stages. The results indicated that overexpression of PRDX3 was associated with 94.9% HCC, and correlated with poor differentiation (P<0.05), which suggest that PRDX3 has substantial clinical impact on the progression of hepatocarcinoma, and may be a potential therapeutic target for HCC.

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“…Studies have demonstrated that resistance to platinum drugs in ovarian cancer cells is linked to mitochondrial dysfunctions in oxidative phosphorylation and energy production (36 -40). Mitochondrial proteomic analysis of drug-resistant cells has shown that five mitochondrial proteins (ATP-a, PRDX3, PHB, ETF, and ALDH) that participate in the electron transport respiratory chain are down-regulated in drug-resistant cell lines (41). PRDX3 is involved in redox regulation of the cell to protect radical-sensitive enzymes from oxidative damage.…”

mentioning

confidence: 99%

Down-regulation of Ras-related Protein Rab 5C-dependent Endocytosis and Glycolysis in Cisplatin-resistant Ovarian Cancer Cell Lines

Jin

Huo

Zheng

et al. 2014

Molecular & Cellular Proteomics

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Drug resistance poses a major challenge to ovarian cancer treatment. Understanding mechanisms of drug resistance is important for finding new therapeutic targets. In the present work, a cisplatin-resistant ovarian cancer cell line A2780-DR was established with a resistance index of 6.64. The cellular accumulation of cisplatin was significantly reduced in A2780-DR cells as compared with A2780 cells consistent with the general character of drug resistance. Quantitative proteomic analysis identified 340 differentially expressed proteins between A2780 and A2780-DR cells, which involve in diverse cellular processes, including metabolic process, cellular component biogenesis, cellular processes, and stress responses. Expression levels of Ras-related proteins Rab 5C and Rab 11B in A2780-DR cells were lower than those in A2780 cells as confirmed by real-time quantitative PCR and Western blotting. The short hairpin (sh)RNA-mediated knockdown of Rab 5C in A2780 cells resulted in markedly increased resistance to cisplatin whereas overexpression of Rab 5C in A2780-DR cells increases sensitivity to cisplatin, demonstrating that Rab 5C-dependent endocytosis plays an important role in cisplatin resistance. Our results also showed that expressions of glycolytic enzymes pyruvate kinase, glucose-6-phosphate isomerase, fructosebisphosphate aldolase, lactate dehydrogenase, and phosphoglycerate kinase 1 were down-regulated in drug resistant cells, indicating drug resistance in ovarian cancer is directly associated with a decrease in glycolysis. Furthermore, it was found that glutathione reductase were up-regulated in A2780-DR, whereas vimentin, HSP90, and Annexin A1 and A2 were down-regulated. Taken together, our results suggest that drug resistance in ovarian cancer cell line A2780 is caused by multifactorial traits, including the down-regulation of Rab 5C-dependent endocytosis of cisplatin, glycolytic enzymes, and vimentin, and up-regulation of antioxidant proteins, suggesting Rab 5C is a potential target for treatment of drug-resistant ovarian cancer. This constitutes a further step toward a comprehensive understanding of drug resistance in ovarian cancer.Molecular & Cellular Proteomics 13: 10.1074/ mcp.M113.033217, 3138-3151, 2014.Ovarian cancer is the major cause of death in women with gynecological cancer. Early diagnosis of ovarian cancer is difficult, while its progression is fast. The standard treatment is surgical removal followed by platinum-taxane chemotherapy. However, the efficacy of the traditional surgery and chemotherapy is rather compromised and platinum resistant cancer recurs in ϳ25% of patients within six months, and the overall five-year survival rate is about 31% (1-3). Virtually no efficient second line treatment is available. In order to increase survival rates from ovarian cancer and enhance patients' quality of life, new therapeutic targets are urgently required, necessitating a deeper understanding of molecular mechanisms of drug resistance.Mechanisms of drug-resistance in ovarian cancer have been extensi...

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Mitochondrial comparative proteomics of human ovarian cancer cells and their platinum‐resistant sublines

Cited by 55 publications

References 50 publications

Serum Peroxiredoxin3 is a Useful Biomarker for Early Diagnosis and Assessemnt of Prognosis of Hepatocellular Carcinoma in Chinese Patients

Serum Peroxiredoxin3 is a Useful Biomarker for Early Diagnosis and Assessemnt of Prognosis of Hepatocellular Carcinoma in Chinese Patients

Detection and identification of peroxiredoxin 3 as a biomarker in hepatocellular carcinoma by a proteomic approach

Down-regulation of Ras-related Protein Rab 5C-dependent Endocytosis and Glycolysis in Cisplatin-resistant Ovarian Cancer Cell Lines

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