RESUMO
Matrine is one of the main active components that is extracted from the dry roots of Sophora flavescens. The compound has potent antitumor activity in various cancer cell lines. However, the anticancer activity of matrine in colon cancer cells remains unclear. The purpose of the present study was to investigate the effects of matrine on the growth of human colon cancer cells and the expression of the associated proteins. Cancer cell proliferation was measured by 3-(4,5-dimethylthiazolyl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. The cell cycle distribution and apoptosis were analyzed by flow cytometry (FCM). The activation of the caspases and the expression of pro-apoptotic and anti-apoptotic factors were examined using western blot analysis. Matrine was shown to significantly inhibit the proliferation of HT29 cells in a dose- and time-dependent manner, and also to reduce the percentage of cells in the G2/M phase, which was most frequently associated with an increase of cells arrested in the G0/G1 phase of the cell cycle. Western blot analysis revealed that matrine induced the activation of caspase-3 and -9 and the release of cytochrome C (Cyto C) from the mitochondria to the cytosol. Furthermore, the pro-apoptotic factor, Bax, was upregulated and the anti-apoptotic factor, Bcl-2, was downregulated, eventually leading to a reduction in the ratio of Bcl-2/Bax proteins. The results demonstrated that matrine inhibits proliferation and induces apoptosis of HT29 human cells in vitro. The induction of apoptosis appears to occur through the upregulation of Bax, the downregulation of Bcl-2, the release of Cyto C from the mitochondria to the cytosol and the activation of caspase-3 and caspase-9, which subsequently trigger major apoptotic cascades. Matrine has potent antitumor activity in HT29 cells and may be used as a novel effective reagent in the treatment of colon cancer.
RESUMO
OBJECTIVE: To investigate the feasibility and safety of substituting tacrolimus(FK506) for cyclosporin A(CsA) on delaying the pace of renal dysfunction in patients with biopsy-proven chronic allograft nephropathy(CAN). METHODS: Seventy-three renal transplantation patients with CAN proved by allograft biopsy were collected in this study. Patients were randomly divided into 2 groups. Patients were either converted to FK506(FK506 group, n=43) or remained on their initial CsA-based immunosuppression(CsA group, n=30). The clinical data at study entry and after 12 months including blood urea nitrogen(BUN), serum creatinine(SCr), glomerular filtration rate(GFR), 24-hour urine protein excretion, serum total cholesterol(TC), triglyceride(TG), low density lipoprotein(LDL) and the side effects of calcineurin inhibitors were monitored during a follow-up of over 12 months. RESULTS: Twelve months later, the level of SCr was statistically reduced and GFR levels were obviously elevated in the FK506 group as compared with CsA group [(194.8+/-42.5)micromol/L vs. (245.4+/-52.8)micromol/L and (50.14+/-3.92)mL/(min.1.73 m(2)) vs. (40.58+/-2.49)mL/(min.1.73 m2), P<0.01]. Quantity of 24-hour urine protein excretion in the FK506 group was (2.0+/-0.5)g which is significantly lower than (3.9+/-0.7)g in the CsA group(P<0.01). TC, TG, and LDL levels remained unchanged in the CsA group, while those were statistically reduced in the FK506 group respectively [(5.19+/-0.73)mmol/L vs. (6.94+/-1.37)mmol/L, (1.86+/-0.84)mmol/L vs. (3.14+/-1.38)mmol/L, (3.03+/-0.71)mmol/L vs. (3.82+/-0.89)mmol/L, P<0.01]. Tremor obviously increased (P<0.01) and hypertension obviously decreased (P<0.05) in the FK506 group compared with the CsA group. CONCLUSION: FK506 treatment can greatly improve the proteinuria and hyperlipidemia. Conversion from CsA to FK506 is an effective and safe alternative therapy for delaying the progression of renal dysfunction induced by CAN.