ABSTRACT
<p><b>OBJECTIVE</b>To determine the effect of the combination of lapatinib with chlorogenic acid on metastasis of breast cancer in mouse model.</p><p><b>METHODS</b>The classical macrophage M2 polarization model induced by interlukin13in vitro was adopted in the study. Flow cytometric analysis was performed to detect the expression of M2 marker CD206. The transcription of M2-associated genes was measured by RT-PCR. HE staining was used to analyze the metastatic nodes of breast cancer in lungs of MMTV-PyVT mice. Immunostaining analysis was used to detect the expression of related proteins in breast cancer.</p><p><b>RESULTS</b>The combination of lapatinib and chlorogenic acid inhibited the expression of CD206 induced by IL-13[(42.17%±2.59%) vs (61.15%±7.58%), P<0.05]. The combination more markedly suppressed expression of M2-associated gene Ym1 than lapatinib alone[(0.9±0.1) vs (1.8±0.0), P<0.05]. The combination of lapatinib and chlorogenic acid significantly reduced metastatic nodes in lung[P<0.05], and also significantly decreased the percentage of CD206(+) cells in breast cancer compared to controls[(6.08%±2.60%) vs(29.04%±5.86%), P<0.05].</p><p><b>CONCLUSION</b>The combination of lapatinib and chlorogenic acid can effectively inhibit macrophage M2 polarization and metastasis of breast cancer.</p>
Subject(s)
Animals , Female , Mice , Chlorogenic Acid , Pharmacology , Lung Neoplasms , Drug Therapy , Macrophages , Mammary Neoplasms, Experimental , Drug Therapy , Neoplasm Metastasis , Drug Therapy , Quinazolines , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To evaluate the anti-tumor effect of the combination of suberoylanilide hydroxamic acid(SAHA) with statins(lovastatin or simvastatin) on non-small cell lung carcinoma(NSCLC) cells.</p><p><b>METHODS</b>Human NSCLC A549 cells were treated with SAHA in combination of lovastatin or simvastatin. The cell growth was analyzed by SRB method, and the apoptosis of A549 cells was assessed by flow cytometer. The expression of cleaved poly-ADP-ribose polymerase(cleaved-PARP) and p21 protein was analyzed by Western-blotting when A549 cells were challenged with 2.5μmol/L SAHA and 5μmol/L lovastatin.</p><p><b>RESULTS</b>Lovastatin and simvastatin synergized SAHA in the inhibition of A549 cells. SAHA induced apoptosis was also enhanced by lovastatin. Treatment with 2.5μmol/L SAHA significantly up-regulated the expression of p21 protein in 48 h, while the protein expression was reduced in combined treatment with 5μmol/L lovastatin.</p><p><b>CONCLUSION</b>Statins can synergize the anti-tumor effect of SAHA in human NSCLC cells through a p21-dependent way.</p>
Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Apoptosis , Carcinoma, Non-Small-Cell Lung , Pathology , Cell Line, Tumor , Cell Proliferation , Cyclin-Dependent Kinase Inhibitor p21 , Metabolism , Hydroxamic Acids , Pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Pharmacology , Poly(ADP-ribose) Polymerases , MetabolismABSTRACT
OBJECTIVE@#To investigate the cellular toxicity of isoniazid together with rifampicin and the metabolites of isoniazid on cultured QSG-7701 cells lines.@*METHODS@#Isoniazid, rifampicin, mixture of rifampicin and isoniazid, acetylhydrazine, hydrazine were added in cultural media of QSG-7701 cells and cultured for 48 hours. The survival rate of cells was determined by MTT method. The cultural media and cells were collected and the activity of lactate dehydrogenase was detected by chromatometry.@*RESULTS@#Compared with control group, the survival rate decreased significantly and the lactate dehydrogenase released from cell increased significantly in cells treated with isoniazid, rifampicin, acetylhydrazine, hydrazine. Hydrazine, the metabolite of isoniazid produced significant damage on hepatocytes in low concentration.@*CONCLUSIONS@#Rifampicin together with rifampicin and metabolites of isoniazid produce cellular toxic effects and hydrazine may be the most toxiferous metabolite.
Subject(s)
Humans , Analysis of Variance , Antitubercular Agents , Toxicity , Case-Control Studies , Cell Survival , Cells, Cultured , Chemical and Drug Induced Liver Injury , Drug Combinations , Hepatocytes , Isoniazid , Toxicity , L-Lactate Dehydrogenase , Metabolism , Rifampin , ToxicityABSTRACT
<p><b>AIM</b>To establish the rat model of morphine-induced conditioned place preference (CPP) and to investigate the effects of morphine psychical dependence on the levels of neurosteroids in rat brain.</p><p><b>METHODS</b>Rats were ip administered morphine 5 mg x kg(-1) for 10 days to induce CPP in morphine group. The concentrations of dehydroepiandrosterone (DHEA), pregnenolone (PREG), allopregnanolone (AP), dehydroepiandrosterone sulfate (DS) and pregnenolone sulfate (PS) in nucleus accumbens (Nac), hypothalamus (Ht), amygdale (A) and plasma of rats were determined with liquid chromatography-negative atmospheric pressure ionization mass spectrometry (LC-MS).</p><p><b>RESULTS</b>Trained with morphine for 10 days resulted in the acquisition of CPP in morphine group with the time that the rats spent in drug-pairing room was longer than that of control group. Compared with control group, morphine treatment could significantly decrease the contents of DHEA in Nac and plasma, decrease that of PREG in Ht.</p><p><b>CONCLUSION</b>Morphine could induce the CPP in rats and affected the contents of some neurosteroids in rat brain, which suggests that endogenous neurosteroids might he related to the development of morphine dependence.</p>