ABSTRACT
Objective To investigate the feasibility of tetrandrine combined with paclitaxel (PTX) in multidrug resistance reversal on C6/MDR glioma cells, and explore the potential molecular mechanisms. Methods Through the comparison of non-resistant glioma C6 cells and drug-resistant glioma C6/MDR cells, the cytotoxicity of against C6/MDR (or C6) cells were assayed by MTT method. The intracellular accumulation of PTX and Rhodamine 123 (R123) were determined by high performance liquid chromatography (HPLC) and flow cytometry, respectively. The cell apoptosis induction of C6/MDR (or C6) cells was detected by AnnexinV-PE/7-AAD staining method after various intervention of PTX, tetrandrine, and PTX + HfA. P-glycoprotein (P-gp) expression and P-gp ATPase activity were evaluated through P-gp antibody binding assay kit and Pgp-GloTM assay systems, respectively. Results The half maximal inhibitory concentration (IC50) of tetrandrine + PTX against C6/MDR cells were (5.88 ± 0.43) nmol/L. The C6/MDR intracellular accumulation of PTX and R123 were increased by 9.4-fold and 12.3-fold in the presence of 10 μmol/L tetrandrine. Accordingly, the apoptosis rate of C6/MDR cells treated with tetrandrine + PTX was 2.3-fold higher than PTX treatment. The tetrandrine-mediated multidrug resistance reversal was involved with the downregulation of P-gp expression and the stimulation of P-gp ATPase activity. Conclusion The combination of tetrandrine and PTX had a potential of overcoming multidrug resistance on C6/MDR glioma cells in vitro.
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OBJECTIVE: To prepare a redox and pH dual sensitive nano-carrier based on PAMAM in order to co-loading chemotherapeutics doxorubicin and breast cancer multidrug resistance reversal agent elacridar, and study their in vitro reversal effect. METHODS: The infrared spectrum FTIR was used to characterize the carrier. Confocal was used to investigate the intracellular triggered drug release. The reversal effect of breast cancer multidrug resistance and the in vitro anti-tumor activity of doxorubicin and elacridar co-loaded nanoparticles were investigated using flow cytometry and cell toxicity tests, respectively. RESULTS: The doxorubicin and elacridar co-loaded nanoparticles (PSSP/DOX/ELC) were successfully prepared, and pH-redox dual sensitive of carrier was proved by cell experiments. And the carrier was uptaken into cells and delivery to lysosome, and drug release was triggered in the lysosome acid condition, then the released drug diffused to the nucleus. The trial of rhodamine 123 accumulation and efflux assay revealed that the accumulation of rhodamine 123 was notably increased after incubation of elacridar in MCF-7/ADR cells. The cytotoxicity of PSSP/DOX/ELC nanoparticles against MCF-7/ADR cell line was significantly stronger than that of either free doxorubicin or only doxorubicin loaded nanoparticles (PSSP/DOX). CONCLUSION: The reversal effect of multidrug resistance and the cytotoxicity of cancer cells were significantly enhanced by PSSP/DOX/ELC nanoparticles. PSSP/ DOX/ELC nanoparticles is a promising delivery system.
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Objective To investigate the reversal of the multidrug resistant gene mdr1 in vivo by antisense oligodeoxynucleotide (ASODN) on the basis of study in vitro. Methods The cultured drug-resistant human hepatocellular carcinoma cells were injected under the skin of axilla to establish the tumor model of nude mice. mdr1 ASODN accompanied by Lipofectamine were injected locally and ADM was injected intraperitoneally. Control 1 and control 2 were locally injected by Lipofectamine and normal saline separately, and ADM was also injected intraperitoneally. Results As time went on the tumor size increased and from the 5th day on alterations were marked, tumor size in different time phase showed marked difference to the prior time phase with significant difference (P 0.05). The results suggested that SODN and Lipofectamine showed no marked effect on tumor growth of nude mice and ASODN had marked inhibition effect on tumor growth.Conclusion mdr1 ASODN can also reverse multidrug resistance of drug-resistant human hepatocellular carcinoma cells in vivo. After the treatment the tumor’s growth in nude mice will slow down in a range of time.