The overexpression of ABC transporters induced by anticancer drugs has been found to be the main cause of multidrug resistance. It is actually also a strategy by which cancer cells escape being killed. Tetrandrine is a natural product extracted from the stem of Tinospora crispa. In this study, tetrandrine showed synergistic cytotoxic activity in combinational use with chemotherapeutic drugs, such as Doxorubicin, Vincristine, and Paclitaxel, in both drug-induced and MDR1 gene-transfected cancer cells that over-expressed ABCB1/P-glycoprotein. Tetrandrine stimulated P-glycoprotein ATPase activity, decreased the efflux of [³H]-Paclitaxel and increased the intracellular accumulation of [³H]-Paclitaxel in KB-C2 cells. Furthermore, SW620/Ad300 and KB-C2 cells pretreated with 1 μM tetrandrine for 72 h decreased P-glycoprotein expression without changing its cellular localization. This was demonstrated through Western blotting and immunofluorescence analysis. Interestingly, down-regulation of P-glycoprotein expression was not correlated with gene transcription, as the MDR1 mRNA level exhibited a slight fluctuation in SW620/Ad300 and KB-C2 cells at 0, 24, 48, and 72 h treatment time points. In addition, molecular docking analysis predicted that tetrandrine had inhibitory potential with the ABCB1 transporter. Our results suggested that tetrandrine can antagonize MDR in both drug-selected and MDR1 gene-transfected cancer cells by down regulating the expression of the ABCB1 transporter, followed by increasing the intracellular concentration of chemotherapeutic agents. The combinational therapy using tetrandrine and other anticancer drugs could promote the treatment efficiency of drugs that are substrates of ABCB1.

Establishing thrombosis‐resistant surface is crucial to develop tissue‐engineered small diameter vascular grafts for arterial reconstructive procedures. The objective of this study was to evaluate the stability and anti‐coagulation properties of heparin covalently linked to decellularized porcine carotid arteries. Cellular components of porcine carotid arteries were completely removed with chemical and physical means. Heparin was covalently linked to the decellularized vessels by a chemical reaction of the carboxyl end of amino acids with hydroxylamine sulphate salt and heparin‐EDC. Bound heparin contents were measured by quantitative colorimetric assay of toluidine blue staining. The average content of heparin in treated vessels was 35.6 ± 11.6 mg/cm² tissue, which represented 6.21 ± 2.03 UPS heparin/cm² tissue. The stability of heparin linkage was tested by incubating the heparin‐linked vessels either in PBS at 37°C or in 70% alcohol at room temperature up to 21 days, showing no significant reduction of heparin content. Anti‐coagulation property of bound heparin was determined with a clotting time assay using fresh dog blood. Standardized small pieces of non‐heparin‐bound vessels were clotted in fresh dog blood within 10 min., whereas all heparin‐bound vessels did not form clot during 1‐hr observation. In vivo platelet deposition of the vessel was determined with a baboon model of the femoral arteriovenous external shunt and ¹¹¹Indium labelling of platelets. There were 1.38 ± 0.07 × 10⁹ and 0.64 ± 0.11×10⁹ baboon platelets deposited on the control and heparin‐linked vessels, respectively, at 60 min. These data demonstrate that covalent linkage of heparin provides an effective and stable anti‐coagulation surface of decellularized porcine carotid arteries. This study may suggest a new strategy to develop tissue‐engineered biological vascular grafts, which could be used for human coronary or low extremity artery bypasses.

AIM:To compare the effect of polyherbal medicine and single herb of Chuang herb HanYiTai in resisting HBV by detecting HBV antigen and HBV DNA.METHODS:Different concentrations of HanYiTai and other compounded herbs were co-incubated with 2215 cells in vitro,and their toxic effects were detected by XTT method to determine the safe concentrations of HanYiTai and other herbs.Polyherbal compounds were matched with a variety of intoxic concentrations of herbs.Culture medium was changed once every 3 d,and supernatants were collected 9 d later.The contents of HBsAg and HBeAg in supernatants were measured using ELISA.Meanwhile,the secretion of HBV-DNA was detected using fluorescent quantitative PCR.RESULTS:The inhibitory effect of polyherbal medicine on the secretion of HBsAg antigen was slightly stronger than that of single HanYiTai group,but the difference was not statistically significant.The inhibitory effect of polyherbal medicine F3-F5 on the secretion of HBeAg and HBVDNA was significantly stronger than that of corresponding concentrations of single HanYiTai(P = 0.002-0.009;P = 0.038-0.05).Polyherbal medicine at low and middle concentrations(F3-F5) showed stronger inhibitory effect on the secretion of HBVDNA than that at high concentrations(F1-F2)(P = 0.048-0.015).CONCLUSION:Anti-HBV effect of low concentration of polyherbal medicine was better than that of high concentration of polyherbal medicine and corresponding concentration of HanyiTai single herb.The mutual influence and synergy of various pharmaceutical ingredients can not only reduce the concentration of a single drug but also produce a superimposed synergistic effect.