Zuo Jin Wan reverses P-gp-mediated drug-resistance by inhibiting activation of the PI3K/Akt/NF-κB pathway.

BACKGROUND: Zuo-Jin-Wan (ZJW), a traditional Chinese medicine formula, has been identified to be effective against drug resistance in cancer. In the present study, we investigated the effect of ZJW on acquired oxaliplatin-resistant and the PI3K/Akt/NF-κB pathway in vitro. METHODS: We tested the dose-response relationship of ZJW on reversing drug-resistance by CCK-8 assay and flow cytometry analysis in vitro. The protein expression of P-gp, MRP-2, LRP, and ABCB1 mRNA expression level were evaluated by Western blot and quantitative RT-PCR. The activities of PI3K/Akt/NF-κB pathway were also examined with or without ZJW, including Akt, IκB, p65 and their phosphorylation expression. RESULTS: We found that ZJW significantly enhanced the sensitivity of chemotherapeutic drugs and increased oxaliplatin (L-OHP)-induced cell apoptosis in a time- and dose-dependent manner. Moreover, both ZJW and a PI3K specific inhibitor (LY294002) suppressed phosphorylation of Akt (Ser473) and NF-κB, which is necessary in the activation of the PI3K/Akt/NF-κB pathway. The effect of ZJW in reversing drug-resistance and suppressing phosphorylation of Akt (Ser473) and NF-κB were weakened after treatment with a PI3K/Akt activator in HCT116/L-OHP cells. CONCLUSIONS: Our study has provided the first direct evidence that ZJW reverses drug-resistance in human colorectal cancer by blocking the PI3K/Akt/NF-κB signaling pathway, and could be considered as a useful drug for cancer therapy.

Zuo Jin Wan, a Traditional Chinese Herbal Formula, Reverses P-gp-Mediated MDR In Vitro and In Vivo.

Zuo Jin Wan (ZJW), a typical traditional Chinese medicine (TCM) formula, has been identified to have anticancer activity in recent studies. In this study, we determined the underlying mechanism of ZJW in the reversal effect of multidrug resistance on colorectal cancer in vitro and in vivo. Our results showed that ZJW significantly enhanced the sensitivity of chemotherapeutic drugs in HCT116/L-OHP, SGC7901/DDP, and Bel/Fu MDR cells. Moreover, combination of chemotherapy with ZJW could reverse the drug resistance of HCT116/L-OHP cells, increase the sensitivity of HCT116/L-OHP cells to L-OHP, DDP, 5-Fu, and MMC in vitro, and inhibit the tumor growth in the colorectal MDR cancer xenograft model. ICP-MS results showed that ZJW could increase the concentration of chemotherapeutic drugs in HCT116/L-OHP cells in a dose-dependent manner. Furthermore, we showed that ZJW could reverse drug resistance of colorectal cancer cells by decreasing P-gp level in vitro and in vivo, which has been represented as one of the major mechanisms that contribute to the MDR phenotype. Our study has provided the first direct evidence that ZJW plays an important role in reversing multidrug resistance of human colorectal cancer and may be considered as a useful target for cancer therapy.

[Analyze the antibody level of enterovirus 71 about children cases of hand-foot-mouse disease outbreak].

OBJECTIVE: To analyze the Enterovirus 71 infectious status about probably cases of hand-foot-mouse disease (HFMD). METHODS: Collect the blood samples of HFDM children probably cases and test the IgG, IgM antibody by ELISA, analyzed the age and gender distribution. RESULTS: We collected 159 blood samples of children probably cases who are 1 to 5 years old. The average EV71 IgG positive rate is 63.5%, which of IgM is 12.0%. The positive rate of EV71 IgG is decrease by aged. Male's EV71 IgM positive rate is higher than female's significantly. CONCLUSION: The pathogen of this case of HFMD outbreak is EV71. Male's EV7l infectious and incidence are higher than female's. The result of this investigation could provide information to HFMD disease control.

Simultaneous determination of 42 organic chemicals in bottled water by combining C18 extraction disk with GC-MS and LC/MS/MS technique.

A method for the determination of 42 hazard residues required by 'Japan Positive List System' in bottled water was described. Hazard compounds in bottled water were extracted with a solid phase extraction step using C18 disks. Determination was carried out by gas chromatography/mass spectrometry (GC/MS) and liquid chromatography-tandem mass spectrometry (LC/MS/MS). The disk extraction has high throughput which is well adapted to isolate and enrich these compounds from large volumes of water. For the water sample spiked at three concentration levels (LOQ, 4 times LOQ and 8 times LOQ), the recoveries of all analytes ranged between 65% and 120% with a relative standard deviation<24% (n=8).