ABSTRACT
Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler (LCD) for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency.
ABSTRACT
@#ObjectiveTo identify the differences between acetylcholine(Ach)-induced increase and adenosine triphosphate(ATP)-induced increase in cytosolic free Ca2+ concentration ([Ca2+]c) in mouse pancreatic β-cells. MethodsMouse pancreatic β-cells were primarily cultured and divided into two groups,one group was stimulated by Ach and another by ATP.[Ca2+]c was recorded with Fura-2 in normal condition, chelation of extracellular Ca2+ by EGTA and depletion of intracellular Ca2+ stores by Thapsigargin.ResultsAch induced a transient peak increase and sustained increase in [Ca2+]c. ATP induced a transient peak increase and no sustained increase. Chelation of extracellular Ca2+ by EGTA eliminated the sustained increase induced by Ach, and did not eliminate the transient peak increase induced by Ach and ATP. Depletion of intracellular Ca2+ stores by Thapsigargin eliminated the transient peak increase induced by Ach and ATP and the sustained increase induced by Ach. ConclusionsAch induces intracellular Ca2+ release and the following Ca2+ release-activated Ca2+ influx, and ATP induces intracellular Ca2+ release, but blocks the following Ca2+ release-activated Ca2+ influx.
ABSTRACT
@#ObjectiveTo identify the influence of cholesterol on insulin-secreting cells.Methods MIN6 mouse insulin cells were cultured in vitro. After confluence of cells, on one hand, free cholesterol in series concentrations was added to cultu re medium to act for 24 hours, and on the other hand, free cholesterol in same c oncentration was added to culture medium to act for different periods. MTT test was used to evaluate the viability of MIN6 cells.Results25μmol/L free cholesterol significantly decreased the viability of MIN6 c ells after 24 hours and 100μmol/L free cholesterol significantly decreased the viability of MIN6 cells after 12 hours and induced cells death after 24 hours.Conclusions Free cholesterol decreases viability of MIN6 cells in a dose-dependent and time-dependent manner, and it is indicated that elevated free cholesterol concentration in blood may be one factor involved in the dysfunction of pancreatic β-cells.
ABSTRACT
Objective:To investigate the effect of cyclopamine on growth and proliferation of human mammary carcinoma cell line Bcap-37.Methods:The Bcap-37 cells were incubated with cyclopamine,which is the specific inhibitor of Hedgehog signaling pathway.Then the inverted microscope was used to observe the morphologic changes of the cells,and MTT assay,BrdU incorporation and cell cycle analysis were used to examine the influence of cyclopamine on Bcap-37 cell growth and DNA synthesis.Results:Compared with the control group,after the cells were incubated with cyclopamine,obvious morphologic changes of Bcap-37 cells were observed;the growth of Bcap-37 cell was inhibited in a dose and time dependent manner;the DNA synthesis of Bcap-37 cells was obviously inhibited;the number of Bcap-37 cells in S phase decreased and the cells were blocked in G2 phase.Conclusion:Cyclopamine can effectually inhibit the growth and proliferation of Bcap-37 cells,which indicates that Hedgehog signaling pathway may be inappropriately activated in breast cancer and inhibiting Hedgehog signaling pathway can be a useful method in breast cancer treatment.
ABSTRACT
Objective:To elucidate the signal transduction mechanism of the modulation of immune cells by estrogen,the effect of 17?-estradiol(E2)on the production of nitric oxide (NO)from spleen mononuclear cells(MNC)of rats and the expression of inductible NO synthase(iNOS) in estrogen receptor(ER) knockout mice were examined.Methods:Culture of the spleen MNC from normal,Freund's incomplete adjuvant(FIA)or myelin basic protein(MBP) immunized Lewis rats.Detection NO production in the supernatant of culture was determined by Griess reagent.The expression of iNOS in spleen sections were observed by immunofluorescence staining.Results:①E2 dose-dependently induce NO production in spleen MNC from normal rats,MNC from FIA or MBP immunized rats manifest in the same manner.iNOS INHIBITOR l-NAME or MAPK blocker could suppress the induction.②In vivo E2 enhanced iNOS expression in wild type mice(WT),but had no effect in ER ? knockout mice(EPKO).ER? knockout mice(BERKO)appear the same with wt.Conclusion:E2 could modulate the immune system via induction of NO,which involves both genomic and nongenomic mechanisms.
ABSTRACT
AIM To investigate the effect of tamoxifen on the proliferation of the anterior pituitary cell of rats and its mechanism. METHODS Primary culture of the anterior pituitary cell of rats and 3H TdR incorporation method were applied. The changes of cell morphology were observed directly by electric microscope. RESULTS Tamoxifen could inhibit the proliferation of the anterior pituitary cell of rats. The inhibitory effect of tamoxifen (0 1 ?mol?L -1 ) could be reversed by estrogen.The classical apoptotic changes appeared in the cells after tamoxifen incubation for 48 h. CONCLUSION Tamoxifen can inhibit the proliferation of the anterior pituitary cell of rats and resultin the cell apoptosis.