Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 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

Using an adenoviral system as a delivery mediator of therapeutic gene, we investigated the therapeutic effects of the use of combined MDR1 shRNA and human NIS (hNIS) radioiodine gene therapy in a mouse colon xenograft model. In vitro uptake of Tc-99m sestamibi was increased approximately two-fold in cells infected with an adenovirus vector that expressed MDR1 shRNA (Ad-shMDR1) and I-125 uptake was 25-fold higher in cells infected with an adenovirus vector that expressed human NIS (Ad-hNIS) as compared with control cells. As compared with doxorubicin or I-131 treatment alone, the combination of doxorubicin and I-131 resulted in enhanced cytotoxicity for both Ad-shMDR1- and Ad-hNIS-infected cells, but not for control cells. In vivo uptake of Tc-99m sestamibi and Tc-99m pertechnetate was twofold and 10-fold higher for Ad-shMDR1 and Ad-hNIS-infected tumors as compared with tumors infected with a control adenovirus construct that expressed beta-galactosidase (Ad-LacZ), respectively. In mice treated with either doxorubicin or I-131 alone, there was a slight delay in tumor growth as compared to mice treated with Ad-LacZ. However, combination therapy with doxorubicin and I-131 induced further significant inhibition of tumor growth as compared with mice treated with Ad-LacZ. We have shown successful therapeutic efficacy of combined MDR shRNA and hNIS radioiodine gene therapy using an adenoviral vector system in a mouse colon cancer model. Adenovirus-mediated cancer gene therapy using MDR1 shRNA and hNIS would be a useful tool for the treatment of cancer cells expressing multi-drug resistant genes.
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PMID:Enhanced anti-tumor effects of combined MDR1 RNA interference and human sodium/iodide symporter (NIS) radioiodine gene therapy using an adenoviral system in a colon cancer model. 2018 72