Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drug resistance acquired by cancer cells has led to treatment failure. To understand the regulatory network underlying docetaxel resistance in breast cancer cells and to identify molecular targets for therapy, we tested small interfering RNAs (siRNAs) against 36 genes whose expression was elevated in human nonresponders to docetaxel for the ability to promote apoptosis of docetaxel-resistant human breast cancer cells (MCF7-ADR cells). The results indicate that the downregulation of the gene encoding ribophorin [corrected] II (RPN2), which is part of an N-oligosaccharyl transferase complex, most efficiently induces apoptosis of MCF7-ADR cells in the presence of docetaxel. RPN2 silencing induced reduced glycosylation of the P-glycoprotein, as well as decreased membrane localization, thereby sensitizing MCF7-ADR cells to docetaxel. Moreover, in vivo delivery of siRNA specific for RPN2 markedly reduced tumor growth in two types of models for drug resistance. Thus, RPN2 silencing makes cancer cells hypersensitive response to docetaxel, and RPN2 might be a new target for RNA interference-based therapeutics against drug resistance.
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PMID:RPN2 gene confers docetaxel resistance in breast cancer. 1872 78

Preoperative chemotherapy, often using docetaxel and cisplatin, is a famous treatment option for advanced gastric cancer in Japan. But, there are no effective biomarkers that predict the therapeutic outcome on gastric cancer. Ribophorin II (RPN2) silencing, which decreases glycosylation of P-glycoprotein (P-gp) and membrane localization, restores the sensitivity to docetaxel and cisplatin. We inquired whether RPN2 expression in advanced gastric cancer biopsy tissues may be a predictive biomarker for docetaxel and cisplatin combination preoperative chemotherapy. We judged RPN2 expression immunohistochemically in upper endoscopic biopsy tissues from 40 advanced gastric cancer patients, who received the combination preoperative chemotherapy of docetaxel and cisplatin and gastrectomy with D2 resection during 2008-2014, and compared clinicopathological effects between RPN2-positive and RPN2-negative groups. We also examined sensitivity of RPN2-knockout gastric cancer cells by genome editing to docetaxel and cisplatin. RPN2 expression was observed in 19 of 40 gastric cancer cases. The RPN2-negative group had better clinicopathological responses to docetaxel and cisplatin combination chemotherapy than the RPN2-positive group, especially, in assessment of the histopathological criteria to preoperative chemotherapy. And RPN2-negative group had a significantly higher overall survival and progression-free survival compared to the RPN2-positive group. We also found RPN2-knockout to change docetaxel and cisplatin sensitivity in vitro. RPN2 expression in upper endoscopic biopsy tissues can be an effective predictive biomarker for the treatment outcome to docetaxel and cisplatin combination preoperative chemotherapy in advanced gastric cancer.
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PMID:RPN2 is effective biomarker to predict the outcome of combined chemotherapy docetaxel and cisplatin for advanced gastric cancer. 2963 37

Multidrug resistance (MDR) is a critical reason of cancer chemotherapy failure. Ribophorin II (RPN2) has emerged as a vital regulator of MDR in multiple cancers including gastric cancer (GC). However, the roles and molecular mechanisms of RPN2 in MDR have not been well featured till now. The present study aimed to explore the roles and molecular mechanisms of RPN2 in MDR of drug-resistant GC cells. Results showed that the expressions of RPN2, multidrug resistance 1 (MDR1), and ATP binding cassette subfamily G member 2 (ABCG2) were upregulated in SGC7901/DDP and SGC7901/VCR cells. Knockdown of RPN2 alleviated MDR through downregulating MDR1 and ABCG2 expressions in SGC7901/DDP and SGC7901/VCR cells. RPN2 depletion inhibited the activation of MEK/ERK pathway. RPN2 overexpression enhanced MDR by upregulating P-glycoprotein (P-gp) and ABCG2 protein expressions in SGC7901/DDP or SGC7901/VCR cells, while this effect of RPN2 was abrogated by ERK knockdown or treatment with ERK inhibitor PD98059. Our findings suggested that RPN2 potentiated P-gp- and ABCG2-mediated MDR via activating MEK/ERK pathway in GC, hinting the critical values of RPN2 in ameliorating MDR and providing a promising target for GC therapy.
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PMID:Ribophorin II potentiates P-glycoprotein- and ABCG2-mediated multidrug resistance via activating ERK pathway in gastric cancer. 3071 May 84