Molecular mechanism of γ-aminobutyric acid inhibitory on the growth of cholangiocarcinoma QBC939 cell line / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the molecular mechanism of γ-aminobutyric acid (GABA) inhibitory on the growth of cholangiocarcinoma cell line (QBC939).</p><p><b>METHODS</b>QBC939 cells were cultured in different groups and treated with GABA, GABA + bicuculine (A receptor antagonist), GABA + phaclofen (B receptor antagonist) for 48 hours. MTT assay was used to determine the proliferation of QBC939 cells. Annexin V-FITC/PI binding assay was used to detect apoptosis in the QBC939 cells. Western blot was applied to check the expression of signal transducer and activator of transcription 3 (STAT3) and phosphorylation-STAT3 (p-STAT3) proteins in different groups of QBC939 cells. Animal models of cholangiocarcinoma bearing nude mice were established by subcutaneous injection of QBC939 cells and randomized into 2 groups: control and GABA-treated groups. The effect of GABA was evaluated after 5 weeks, including the body weight and tumor volume. The expression of p-STAT3 was detected by immunohistochemistry and Western blot in xenograft tumors.</p><p><b>RESULTS</b>MTT and FCM assays both showed that the effect of GABA inhibitory on the proliferation (15.30% ± 0.80% vs. 2.66% ± 0.74%, t = 23.15, P = 0.00) and induced apoptosis (23.15% ± 0.21% vs. 4.30% ± 0.69%, t = 52.40, P = 0.00) of QBC939 cells could be antagonized by phaclofen, but not bicuculine. The expression of STAT3 and p-STAT3 proteins were all observed in the QBC939 cells and GABA significantly down-regulated p-STAT3 protein expression (0.77 ± 0.00 vs. 0.45 ± 0.01, t = 63.14, P = 0.00), this action was also antagonized by phaclofen (0.45 ± 0.01 vs. 0.76 ± 0.01, t = 56.25, P = 0.00). Xenograft tumor volume ((0.62 ± 0.03) cm³ vs. (0.34 ± 0.03) cm³, t = 13.45, P = 0.00) and the expression of p-STAT3 protein were significantly decreased in GABA-treated group as compared with control group.</p><p><b>CONCLUSIONS</b>GABA may inhibit the growth of cholangiocarcinoma cells QBC939 through GABA(B) receptor, and down-regulation of the p-STAT3 expression perhaps is one of its anti-tumor mechanisms.</p>

Tissue distribution of three chrysophanol formulations in mice / 中国药学杂志

OBJECTIVE: To study the tissue distribution differences of chrysophanol loaded polybutylcyanoacrylate nanocapsules, ehrysophanol-hydroxypropyl-β-cyclodextrin inclusion complex, chrysophanol liposomes in mice, through the tissue distribution of chrysophanol formulations to understand the pharmacodynamic properties of the formulations. With a view to electing for brain targeting the most strong, effect of chrysophanol best formulation. METHODS: Mice tail intravenous injection of the equivalent dose of 10 mg · kg-1 chrysophanol formulations, by 0.25, 1, 2, 4, 8, 12 h taking different points of mice heart, liver, spleen, lungs, kidneys, brain and blood plasma, after playing homogenized the protein processing using HPLC for the determination of chrysophanol in organizations of distribution. Chrysophanol was analyzed on a Thermo Hypersil ODS2 chromatographic column with mobile phase methanol-water(90:10) at 1.0 mL · min-1 flow rate and with column temperature 30°C. The wavelength of UV detector was set at 254 nm and injection volume was 20 μL. RESULTS: Three kinds of chrysophanol formulations could prolong the elimination of time in vivo, and better targeting of tissues and organs than chrysophanol N, N-DMF solution. CONCLUSION: Three kinds of chrysophanol formulations compared to tissue distribution, chrysophanol liposomes in various tissue distribution better, brain tissue targeting the most significant. Chrysophanol liposomes is expected to become the treatment of cerebrovascular disease clinical application of new dosage forms.