English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

AIM: to construct the microsphere, in which recombinant adenovirus (rAdV) was encapusulated, carrying antisense multidrug resistance-associated protein (MRP) gene (asmrp) and to investigate its effect on reversing MRP-mediated mutidrug resistance of hepatocellular carcinoma. METHODS: The microsphere was constructed with biodegradable poly-DL-lactide-poly (ethylene-glycol) encapsulating as-mrp rAdV, and its diameter, the encapsulating rate, the virus loads and the releasing kinetics were determined in vitro. Human hepatocellular carcinoma HepG2/ADM cells were transfected with the microspheres, and the fluorescence intensity was assayed after 48 hours and 120 hours. IC50 of adriamycin on drug-resistant cells was determined. The level of MRP mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR), and the ratio of MRP mRNA to β-actin mRNA (MRP/β-actin) was calculated. Intracelluar rubidomycin (DNR) concentration was examined by flow cytometry. Wistar rats were implanted with Walker-256 tumor solid piece to establish a liver cancer model. After injected with rAdV, the tumor size, growth rate and the average survival time were determined. RESULTS: The microsphere, in which as-mrp rAdV was encapusulated, was constructed successfully. Its diameter, the encapsulating rate and the virus loads were 1.765 μm, 52.4% and 5.5×10efu/g, respectively. Almost 50% of the viruses were released within 120 h, and the total releasing time lasted more than 240 h. The released viruses remained active. More than 90% HepG2/ADM cells could be transfected with 10 mg microspheres. IC50 of adriamycin on HepG2/ADM cells 48 and 120 h after transfection were 9.72 and 4.15 ug, respectively. Intracellular DNR intensity of the cells 120 h after transfection was significantly higher than that 48 h after transfection and the non-transfected cells (168.6±6.97 vs 98.39±6.17, t = 13.68, P < 0.01; 168.6±6.97 vs 112.52±9.21, t = 9.69, P <0.01). The values of MRP/β-actin 120 and 48 h after transfection were decreased by 16.7% and 63.6% respectively as compared with that before transfection, and the value after 120 h was decreased by 26.25% as compared with that after 48 h. Compared with control group, normal saline group, rAdv group and microsphere without rAdv group, the tumor growth rate was decreased significantly in rAdv microsphere group (0.96±0.25 vs 8.79±0.34, 4.82±0.30, 4.67±0.67, 2.97±0.29; P <0.05).The mean life time was prolonged significantly (43.6±7.4 vs 23.4±3.2, 25.3±3.7, 26.5±4.1, 33.7±2.9; P <0.05). CONCLUSION: The microsphere, in which rAdV carrying antisense MRP was encapusulated, can effectively inhibit MRP expression and improve the sensitivity of drug-resistant cells. This provides an experimental basis for the combination of macromolecular chemistry and gene therapy in the treatment of hepatocellular carcinoma.

shijie huaren xiaohua zazhi

Construction of microsphere encapusulating recombinant adenovirus with antisense multidrug resistance-associated protein gene and its effect on hepatocellular carcinoma