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)

Overexpression of the multidrug resistance 1 (MDR1) gene, encoding P-glycoprotein (P-gp), facilitates resistance to diverse chemotherapeutic drugs and current P-gp inhibitors display high toxicity. We studied the effects of melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24), which exhibits cancer-specific apoptosis-inducing properties, in drug-sensitive (SW620) and drug-resistant (SW620/Dox) colorectal carcinoma cells. Adenovirus administered mda-7/IL-24, Ad.mda-7, effectively reversed resistance to doxorubicin-induced apoptosis in SW620/Dox cells by increased intracellular accumulation and decreased efflux of doxorubicin. Unexpectedly, P-gp-overexpressing cells (SW620/Dox) displayed increased apoptosis following Ad.mda-7 infection compared with parental SW620 cells, which correlated with more MDA-7/IL-24 protein in SW620/Dox than SW620 cell and potentially explains the increased sensitivity of P-gp-overexpressing cells to mda-7/IL-24. Transient overexpression of MDR1 in SW620 cells significantly increased apoptosis, decreased anchorage-independent growth, and increased MDA-7/IL-24 protein following Ad.mda-7 infection, whereas down-modulation of MDR1 in SW620/Dox cells by small interfering RNA decreased apoptosis following Ad.mda-7 infection. The increased mda-7/IL-24 sensitivity observed in SW620/Dox cells was partly due to increased reactive oxygen species generation and lower mitochondrial membrane potential. These findings confirm that mda-7/IL-24 is a potent MDR reversal agent, preferentially causing apoptosis in P-gp-overexpressing MDR cells, suggesting significant expanded clinical implications for the use of mda-7/IL-24 in treating neoplasms that have failed chemotherapy mediated by the P-gp MDR mechanism.
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PMID:Melanoma differentiation associated gene-7/interleukin-24 reverses multidrug resistance in human colorectal cancer cells. 1802 83

Gliomas are the most common form of primary brain tumor with the highest mortality rates. Drug resistance is a major cause of treatment failure in patients with glioma. Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) has been demonstrated to play an important role in drug resistance in human cancer cell lines. However, the reversing effect of mda-7/IL-24 on drug resistance of human glioma is not fully clear. Here, we investigated the effects of overexpression of the mda-7/IL-24 gene in human glioma. We established a cisplatin-resistant U87 glioma cell line and found that mda-7/IL-24 was highly correlated with drug resistance. Furthermore, we investigated the apoptotic rate, intracellular accumulation of Rhodamine-123, and expression of glutathione and P-glycoprotein. The over-expression of mda-7/IL-24 enhanced cisplatin cytotoxicity and reversal of drug resistance in glioma cells. The reversing effect of mda-7/IL-24 on drug resistance was induced mainly through the regulation of drug resistance-related genes and efflux drug pumps. Thus, mda-7/IL-24 can be used as a promising predictive biomarker and potential therapeutic target for chemotherapy in glioma.
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PMID:Is mda-7/IL-24 a potential target and biomarker for enhancing drug sensitivity in human glioma U87 cell line? 2379 95