In vitro intestinal permeability studies, pharmacokinetics and tissue distribution of 6-methylcoumarin after oral and intraperitoneal administration in Wistar rats

ABSTRACT 6-Methylcoumarin (6MC) is a semisynthetic coumarin with important in vitro and in vivo anti-inflammatory activity. In order to continue the pre-clinical characterization of this molecule, in vitro intestinal permeability, plasma profile and tissue distribution after oral administration in rats were studied. The permeability of 6MC was evaluated by the Caco-2 cellular model in both the apical-basal (A-B) and basal-apical (B-A) directions. The pharmacokinetics and biodistribution were evaluated in rats after oral and intraperitoneal administration at doses of 200 mg/kg. Transport experiments with Caco-2 cells showed that 6MC presented high permeability at all concentrations evaluated. This finding suggested that 6MC could be transported across the gut wall by passive diffusion. The plasma concentration-time curve showed that the maximum concentration (Cmax) was 17.13 ± 2.90 µg/mL at maximum time (Tmax) of 30 min for the oral route and Cmax 26.18 ± 2.47 µg/mL at 6.0 min for the intraperitoneal administration, with elimination constant of (Ke ) 0.0070 min-1 and a short life half time of (T1/2 ) lower that 120 min. The distribution study showed that 6MC has high accumulation in the liver, and widespread distribution in all the organs evaluated.

Prepraration of PLGA-PLL-PEG Nanoparticles Simultaneously Loaded with Daunorubicin and Tetrandrine / 中国药学杂志

OBJECTIVE: To prepare PLGA-PLL-PEG nanoparticles simultaneously loaded with daunorubicin (DNR) and tetrandrine (Tet).

Effects of estradiol plus testosterone on the proliferation and apoptosis of breast cancer cell line MCF-7 / 肿瘤

Objective: To study the effects of estradiol plus testosterone on the proliferation and apoptosis of breast cancer cell line MCF-7, and to elucidate the possible mechanism. Methods: The growth of MCF-7 cells treated with estradiol (10-10 mol/L) or testosterone (10-5, 10 -7, 10-9 and 10-11 mol/L) alone or in combination for 24, 48 and 72 h was detected by MTT assay. The cell cycle distribution and the apoptosis rate of MCF-7 cells were determined by flow cytometry (FCM). The expression levels of cyclinD1 and androgen receptor (AR) proteins were examined by FCM. Results: The proliferation ability of MCF-7 cells was elevated after treatment with estradiol, and this effect could be inhibited by a higher concentration of testosterone (10-5 mol/L) while improved by a lower concentration of testosterone (10-9 mol/L). After treatment with estradiol plus testosterone (10-5 mol/L) for 48 h, the G1/S phase transition of MCF-7 cells was accelerated, and the apoptosis rate was increased; the expression level of cyclinD1 protein was increased while no change of AR protein expression was observed. Conclusion: Estradiol combined with testosterone of high concentration can inhibit the proliferation of MCF-7 cells and improve the apoptosis. This effect may be associated with the up-regulation of cyclinD1 expression. Copyright© 2011 by the Editorial Board of Tumor.

The chemotherapy role of vinorelbine with relapsed breast cancer primary cells in vitro / 肿瘤研究与临床

Objective To know the antitumor effect and value of vinorelbine in chemotherapy with relapsed breast cancer.Methods To receive breast cancer tissue from primary and relapsed patients by surgery,then to obtain mammary cancer cells by collagenase.The antitumor effect of 5 chemotherapy drugs with breast cancer cells was measured by culture in vitro and MTT.Results With primary cancer cells from primary breast cancer,the antitumor effect of paclitaxel and docetaxel(sensitivity is 91.04%,92.54% respec- tively) is better than adriamycin,epirubicin and gemcitabine(sensitivity is 73.13%,74.63%,71.64% re- spectively;P

Study on The Effect of Estradiol on Proliferation of Diverse Mammary Primary Cells in Vitro / 中国普外基础与临床杂志

Objective To understand the effect of estradiol in different concentrations on proliferation of diverse mammary primary cells in vitro. Methods The primary cells of cancer tissue, the adjacent tissue to tumors and normal mammary tissue from patiens with breast cancer were obtained using collagenase digesting method. All the tissue samples were cultivated in vitro, and were given estradiol in different concentrations. The effect of estradiol on the proliferation of those primary cells was measured by MTT. Results Estradiol remarkedly promoted the proliferation of primary cells of cancer tissue and peritumor tissue in vitro, whose ER expression were positive. Whereas, the promotion effect of estradiol on the proliferation of normal mammary primary cells was relatively weak, and there was no correlation between the promotion effect with the expression of ER in cancer tissue. Conclusion The risks of occurrence and relapse of breast cancer would increase significantly when the concentration of estradiol is no less than 103 pmol/L in vivo.