乳腺癌耐阿霉素细胞MCF-7/ADR外泌体传递tTG参与MCF-7细胞耐药的研究

目的:研究乳腺癌耐阿霉素细胞MCF-7/ADR通过外泌体传递tTG参与敏感细胞MCF-7耐药的过程。方法:本实验首先培养MCF-7、MCF-7/ADR细胞,然后检测MCF-7、MCF-7/ADR细胞中外泌体的含量,并将外泌体提取后备用。MCF-7/ADR细胞外泌体(EXO/ADR)与MCF-7细胞共培养建立MCF-7的外泌体耐药细胞(MCF-7+EXO/ADR)。使用Western blot法检测MCF-7、MCF-7/ADR、MCF-7+EXO/ADR细胞中的tTG蛋白的表达水平,使用流式细胞术分别检测敏感细胞株外泌体(EXO/S)、耐药细胞株外泌体(EXO/ADR)中tTG的表达水平。使用CCK-8法分别检测MCF-7、MCF-7/ADR、MCF-7+EXO/ADR细胞对阿霉素的敏感性情况。结果:实验结果显示,在EXO/S、EXO/ADR中均可以表达CD63、TSG101,但是较低表达Calnexin。经过流式细胞术检测发现,EXO/S、EXO/ADR中的tTG表达水平分别为(18.3±3.63)%、(46.07±8.31)%,二者tTG的表达有明显差异。经过Western blot检测MCF-7、MCF-7/ADR、MCF-7+EXO/ADR细胞中tTG的表达情况,我们发现MCF-7+EXO/ADR细胞的tTG表达水平较MCF-7细胞升高。MCF-7、MCF-7/ADR和MCF-7+EXO/ADR细胞对阿霉素的IC50分别为(1.91±0.18)μg/mL、(82.11±3.51)μg/mL、(6.16±1.15)μg/mL。结论:MCF-7/ADR细胞可能经分泌外泌体来传递tTG参与MCF-7细胞对阿霉素耐药的过程。

数智时代我国纠纷解决机制——从ADR到ODR

[研究目的]随着信息技术的不断完善,我国电子商务蓬勃发展。与此同时,网络纠纷的增长也随之而来。数智时代民事纠纷呈现出数量多、增速快、标的较小、解决周期短的特点。[研究方法]传统的诉讼解决机制已难以适应数智时代下我国网络纠纷的解决需要,“互联网+”技术的发展及“共建共治共享”网络空间治理格局的不断推进使得在线纠纷解决机制应运而生。我国的在线诉讼及智慧法院建设属于ODR机制在司法领域的应用,ODR突破了传统Online ADR的非诉解纷范畴,实现了司法诉讼的线上审判新模式。企业可以直接通过互联网端进行纠纷申报与处理,避免了线下冲突;平台可以在线收集消费者的投诉信息并进行分类处理,更加高效的掌握自家产品或服务面向市场过程中产生的问题,进而加强企业管理与质量监督,改善工作,有利于将企业的不利影响降到最低。在现实应用中,我国ODR机制仍存在立法缺失、ODR机制执行效率低下、消费者信任不足等一系列问题。[研究结论]对此,应在数智背景下完善关于ODR机制对消费者保护的立法规定、培养人民群众化解矛盾纠纷的新思维范式,促进线上纠纷解决机制的普及度,加强“电子信用”建设、完善保全与救济措施、提升ODR机制的平台建设与人才储备以更好促进我国ODR机制的良性发展。

Influence of adriamycin on changes in Nanog, Oct-4, Sox2, ARID1 and Wnt5b expression in liver cancer stem cells

AIM:To determine the influence of Adriamycin(ADM)on the changes in Nanog,Oct4,Sox2,as well as,in ARID1 and Wnt5b expression in liver cancer stem cells.METHODS:The MHCC97-L and HCCLM3 liver cancer cell lines were selected as the cell models in this study,and were routinely cultured.The 50%lethal dose(LD50)in the cell lines was detected by the MTT assay.Expression changes in liver cancer stem cell related genes(Nanog,Oct-4,Sox2,ARID1,and Wnt5b)were detected by western blot following treatment with ADM(LD50).RESULTS:The LD50 of ADM in MHCC97-L cells was lower than that in HCCLM3 cells(0.4123±0.0236μmol/L vs 0.5259±0.0125μmol/L,P<0.05).Wnt5b and Nanog were expressed in both MHCC97-L and HCCLM3 cells,while only Sox2 was expressed in HCCLM3cells.However,neither ARID1A nor Oct4 was detected in these two cell lines.Genes,related to the stem cells,showed different expression in liver cancer cells with different metastatic potential following treatment with ADM(LD50).Wnt5b protein increased gradually within4 h of ADM(LD50)treatment,while Nanog decreased(P<0.05).After 12 h,Wnt5b decreased gradually,while Nanog increased steadily(P<0.05).In addition,only Sox2 was expressed in HCCLM3 cells with high metastatic potential following ADM(LD50)treatment.The expression of Sox2 increased gradually with ADM(LD50)in HCCLM3 cells(P<0.05).CONCLUSION:ADM increased the death rate of MHCC97-L and HCCLM3 cells,while the growth suppressive effect of ADM was higher in MHCC97-L cells than in HCCLM3 cells.

Synergistic Effect of Hyperthermia and Neferine on Reverse Multidrug Resistance in Adriamycin-resistant SGC7901/ADM Gastric Cancer Cells

Multidrug resistance（MDR） plays a major obstacle to successful gastric cancer chemotherapy.The purpose of this study was to investigate the MDR reversal effect and mechanisms of hyperthermia in combination with neferine（Nef） in adriamycin（ADM） resistant human SGC7901/ADM gastric cancer cells.The MDR cells were heated at 42℃ and 45℃ for 30 min alone or combined with 10 μg/mL Nef.The cytotoxic effect of ADM was evaluated by MTT assay.Cellular plasma membrane lipid fluidity was detected by fluorescence polarization technique.Intracellular accumulation of ADM was monitored with high performance liquid chromatography.Mdr-1 mRNA,P-glycoprotein（P-gp）,γH2AX expression and γH2AX foci formation were determined by real-time PCR,Western blot and immunocytochemical staining respectively.It was found that different heating methods induced different cytotoxic effects.Water submerged hyperthermia had the strongest cytotoxicity of ADM and Nef combined with hyperthermia had a synergistic cytotoxicity of ADM in the MDR cells.The water submerged hyperthermia increased the cell membrane fluidity.Both water submerged hyperthermia and Nef increased the intracellular accumulation of ADM.The water submerged hyperthermia and Nef down-regulated the expression of mdr-1 mRNA and P-gp.The water submerged hyperthermia could damage DNA and increase the γH2AX expression of SGC7901/ADM cells.The higher temperature was,the worse effect was.Our results show that combined treatment of hyperthermia with Nef can synergistically reverse MDR in human SGC7901/ADM gastric cancer cells.

Enhanced myocardial fluorodeoxyglucose uptake following Adriamycin-based therapy: Evidence of early chemotherapeutic cardiotoxicity?

AIM: To analyze changes in myocardial glucose metabolism using fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients treated with adriamycin and to investigate the clinical significance of these changes.METHODS: Considering that FDG-PET scanning has the ability to show changes in glucose metabolism in the myocardium, we retrospectively analyzed the FDGPET studies of 18 lymphoma patients treated with adriamycin-based chemotherapy in both the preand posttherapy setting. Cardiac contractile parameters such as left ventricular ejection fraction were not available for correlation in all patients due to the short duration and the level of cumulative dose administered in these patients during the time of the follow-up FDG-PET study. The change in myocardial glucose utilization was estimated by change in standard uptake values (SUV) in the myocardium.RESULTS: We observed a significant change in SUVmean values in the myocardium (defined as more than change in cardiac SUVmean between pre-and post-chemotherapy PET) in 1 patients, whereas 6 patients did not show any significant cardiac FDG uptake in both preand post-therapy PET scans. Patients were divided into three groups based on the changes observed in myocardial tracer uptake on the followup 18 F-FDG-PET study. Group A (n = 8): showed an increase in cardiac 18 F-FDG uptake in the post-therapy scan compared to the baseline scan carried out prior to starting adriamycin-based chemotherapy. Group B (n = 6): showed no significant cardiac 18 F-FDG uptake in post-therapy and baseline PET scans, and group C (n = 4): showed a fall in cardiac 18 F-FDG uptake in the posttherapy scan compared to the baseline scan. Mean cumulative adriamycin dose (in mg/m 2 ) received during the time of the follow-up FDG-PET study was 256. 25, 250 and 137.5, respectively.CONCLUSION: Our study shows three different trends in the change in myocardial glucose metabolism in patients undergoing adriamycin-based chemotherapy. A further prospective study with prolonged follow-up of ventricular function is warranted to explore the significance of enhanced FDG uptake as a marker of early identification of adriamycin-induced cardiotoxicity.

Protective Effect of Sulodexide on Podocyte Injury in Adriamycin Nephropathy Rats

This study examined the effect of sulodexide on podocyte injury in rats with adriamycin nephropathy （AN）. A total of 36 healthy male SD rats were randomly assigned to three groups： control group, AN group and sulodexide treatment group. Rat models of AN were established by a single tail intravenous injection of adriamycin （6.5 mg/kg） in both AN group and sulodexide treatment group. Sulodexide （10 mg/kg） was administered the rats in the treatment group once daily by garage from the first day of model establishment until the 14th day or the 28th day. Samples of 24-h urine and renal cortex tissues were harvested at day 14, 28 after the model establishment. Excretion of 24-h urinary protein was measured by Coomassie brilliant blue method. The pathological changes in renal tissues were observed by light microscopy and electron microscopy respectively. Heparanase mRNA was detected by RT-PCR. Expressions of desmin, CD2AP and heparanase were determined by immunohistological staining. The results showed that the expressions of heparanase mRNA and protein were increased in the glomeruli of AN rats at day 14 and 28 after the model establishment, which was accompanied by the increased expression of desmin and CD2AP. The mRNA and protein expression of heparanase was decreased in the sulodexide-treated rats as compared with AN rats at day 14 and 28. And, the protein expression of desmin and CD2AP was reduced as with heparanase in the sulodexide-treated rats. Proteinuria and podocyte foot process effacement were alleviated in the AN rats after sulodexide treatment. There was a positive correlation between the expression of heparanase and the expression of desmin and CD2AP （as well as 24-h urinary protein excretion）. It was concluded that increased heparanase is involved in podocyte injury. Sulodexide can maintain and restore podocyte morphology by inhibiting the expression of heparanase in AN.

CdS Quantum Dots as Fluorescence Probes for Detection of Adriamycin Hydrochloride

Water-soluble CdS quantum dots（CdS-QDs） capped with thioglycohc acid were easily prepared, and a detection method of adriamycin was presented based on the fluorescence quenching of CdS-QDs. It was found that a complex could be formed between cetyhrimethyl ammonium bromide（CTAB） and CdS-QDs by using electrostatic interaction in Britton-Robinson（BR） buffer at pH = 7.00, and the strong fluorescence emission of the complex was observed at 500 nm when the complex was excited at 378 run. The presence of adriamycin, however, could strongly quench the fluorescence through hydrophobic interaction. The overall quenching percentage as a function of adriamycin concentration matches the Stern-Volmer equation very well. These properties make CdS-QDs a potential fluorescence probe for the detection of adriamycin. The detection hmit（3σ） of adriamycin is approximately 10^-9 mol/L.

Enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with heart failure induced by adriamycin

Our previous studies have shown that the cardiac sympathetic afferent reflex is enhanced in rats with chronic heart failure （CHF） induced by coronary artery ligation and contributes to the over-excitation of sympathetic ac- tivity. We sought to determine whether sympathetic activity and cardiac sympathetic afferent reflex were en- hanced in adriamycin-induced CHF and whether angiotensin II （Ang II） in the paraventricular nucleus （PVN） was involved in enhancing sympathetic activity and cardiac sympathetic afferent reflex. Heart failure was induced by intraperitoneal injection of adriamycin for six times during 2 weeks （15 mg/kg）. Six weeks after the first injec- tion, the rats underwent anesthesia with urethane and a-chloralose. After vagotomy and baroreceptor denervation, cardiac sympathetic afferent reflex was evaluated by renal sympathetic nerve activity and mean arterial pressure （MAP） response to epicardial application of capsaicin （1.0 nmol）. The response of MAP to ganglionic blockade with hexamethonium in conscious rats was performed to evaluate sympathetic activity. The renal sympathetic nerve activity and cardiac sympathetic afferent reflex were enhanced in adriamycin rats and the maximum depres- sor response of MAP induced by hexamethonium was significantly greater in adriamycin rats than that in control rats. Bilateral PVN microinjection of angiotensin II （Ang II） caused larger responses of the cardiac sympathetic afferent reflex, baseline renal sympathetic nerve activity and MAP in adriamycin rats than control rats. These re- sults indicated that both sympathetic activity and cardiac sympathetic afferent reflex were enhanced and Ang II in the PVN was involved in the enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with adriamycin-induced heart failure.

Protective Effects of Eplerenone on Podocyte Injury in Adriamycin Nephropathy Rats

To investigate the protective effects of eplerenone on adriamycin-induced renal injury and the possible mechanisms involved,36 male Sprague-Dawley rats were randomly divided into control group,adriamycin nephropathy（AN） group and eplerenone-treated group（100 mg.kg-1.d-1 eplerenone）.Blood pressure,24-h urinary protein,serum potassium,sodium and creatinine were measured 28 days after adriamycin injection（a single tail intravenous injection of 6.5 mg/kg adriamycin）.The morphological changes of renal tissues were observed by light and electron microscopy.Immunohistochemistry and Western blotting were performed to examine the expression of TGF-β1 and desmin in renal cortex.The results showed that 28 days after adriamycin injection,there were no significant changes in the level of serum potassium,sodium,creatinine concentrations and blood pressure values in the rats of the three groups.Meanwhile,the 24-h proteinuria excretion in the AN group was significantly higher than that in the control group（P0.01）,but that in the eplerenone-treated group was substantially reduced when compared with that in the AN group（P0.05）.Mild mesangial cell proliferation and matrix expansion,diffuse deformation and confluence of foot processes in podocytes were found in the AN group.By contrast,rats in the eplerenone-treated group exhibited obvious attenuation of these morphological lesions.The protein expression of TGF-β1 and desmin in the AN group was markedly up-regulated in contrast to that in the control group（P0.01）,whereas that in the eplerenone-treated group was much lower than in the AN group（P0.05）.It was concluded that eplerenone may ameliorate the proteinuria and the development of pathological alteration in adriamycin-induced nephropathy presumably via the inhibition of cytokine release,and restore the morphology of podocytes independent of its blood pressure-lowing effects.

The Study on the Relationship between Serum Vascular Endothelial Growth Factor and Proteinuria in Adriamycin induced Nephrotic Rats

To study the relationship between serum vascular endothelial growth factor (VEGF) and proteinuria in adriamycin induced nephrotic rats, a rat model of adriamycin induced nephrotitis was developed by injection of adriamycin into a tail vein in a rat. At different time points, 24 h urinary protein excretion was measured by using Coomassie brilliant blue method and the serum VEGF levels detected by using ELISA assay. The interventional effect of VEGF on this model was observed. The results showed that: (1) The adriamycin induced nephrotic syndrome rat model was developed successfully; (2) Serum VEGF levels and proteinuria were significantly increased at 7th day after intravenous injection of adriamycin. There was a positive correlation between serum VEGF levels and 24 h urinary protein excretion ( r=0.67, P <0.05). (3) The 24 h urinary protein excretion was significantly increased in the rats receiving administration of VEGF ( P <0.05). It was concluded that VEGF might play an important role in the pathogenesis of proteinuria in adriamycin induced nephrotic rats.

Involvement of MMP-2 in Adriamycin Resistance Dependent on ERK1/2 Signal Pathway in Human Osteosarcoma MG-63 Cells

Matrix metalloproteinase-2 (MMP-2) level and the ERK1/2 signal pathway are dependent factors for the growth and metastasis of cancer.However,the impact of MMP-2 in combination with ERK1/2 in tumor patients with drug resistance is unknown.To determine the relationship between MMP-2 and the ERK1/2 signal pathway,we established an adriamycin (ADM)-induced MG-63 (ADM-MG-63) cell line.With the increase of the ERK1/2 pathway blocker PD98059,we detected the expression levels of MMP-2 and p-ERK1/2 by Western blot in ADM-MG-63 cells.In ADM-MG-63 cells transfected with MMP-2-siRNA,the expression of ERK1/2 was detected for understanding the function of the ERK1/2 signal pathway.Three siRNAs for MMP-2 (MMP-2-siRNA) were designed,and the optimal one was selected and tested at different time points of 24,48 and 72 h.Under an ADM-induced condition,ADM-MG-63 cells were finally stable living in the medium of ADM (200 ng/mL).PD98059 could effectively suppress the expression levels of p-ERK1/2 and MMP-2.When the MMP-2 was silenced by using MMP-2-siRNA,the expression of p-ERK1/2 was enhanced.It is con-cluded that MMP-2 may be involved in ADM resistance dependent on ERK1/2 signal pathway,sug-gesting interference in ERK1/2 may be a new method of targeted therapy for tumor resistance.

Preparation of Adriamycin Magnetic Albumin Microspheres and Their Experimental Antitumor Effects in vitro and in vivo

The adriamycin magnetic microspheres (ADM-MAMs) were prepared by the heat-stabilized protein methods. Their physico-chemical properties were examined; their cytotoxicities against tumor cells in vitro were assayed by a modi-fied MTT method, and their effects were observed on the implanted gastric tumor in Wistar rats given ADM-MAMs via alimentary canal at the presence of the ex-ternal magnetic fields. The results showed that the ADM-MAMs were successful-ly prepared and had cytotoxic effect on tumor cells in vitro similar to the free ADM (P>0. 05). The inhibitory effects of ADM-MAMs on the implanted gastric tumor in vivo were significantly increased as compared with the controls (P<0.01). Our results suggested that ADM-MAMs were a new type of adriamycin (ADM) preparation and its form alteration did not affect its anticancer effects.

Treatment of hepatoma with liposome-encapsulated adriamycin administered into hepatic artery of rats

瞄准：加空白与 adriamycin 答案(FADM ) 和 adriamycin 比较在肝细胞瘤上观察包含 liposome 的 adriamycin (LADM ) 的治疗学的效果脂肪一些(ADM + BL ) 管理了进老鼠的肝的动脉。方法：LADM 被 pH 准备坡度驱动的方法。生理盐水， FADM (2 mg/kg ) ， ADM+BL (2 mg/kg ) ，和 LADM (2 mg/kg ) 在忍受肝 W256 癌肉瘤的老鼠经由肝的动脉被注射，它随机被划分成四个组。治疗学的效果以生存时间，肿瘤增大比率，和肿瘤坏死度被评估。差别与 ANOVA 和 Dunnett 测试和木头等级测试被决定。结果：比作 FADM 或 ADM + BL， LADM 生产了更重要的肿瘤抑制(肿瘤体积比率：1.243 +/- 0.523 对 1.883 +/- 0.708， 1.847 +/- 0.661， P 【 0.01 ) ，并且更广泛的肿瘤坏死。增加的寿命在与 FADM 或 ADM+BL 相比收到 LADM 的老鼠显著地被延长(231.48 对 74.66， 94.70 )(P 【 0.05 ) 。结论：肝细胞瘤上的 adriamycin 的反癌症功效能被 liposomal 封装强烈通过肝的动脉的管理改进。

Effects of the Combined Use of Benazepril and Valsartan on Apoptosis in the Kidney of Rats with Adriamycin-induced Nephritic Glomerulosclerosis

Summary: The effects of the combined use of angiotensin converting enzyme inhibitor (ACEI) benazepril and angiotensin Ⅱ type 1 receptor antagonist (AT1RA) valsartan on apoptosis and the expression of apoptosis-related proteins Fas and FasL in the kidney of rats with adriamycin-induced nephritic glomerulosclerosis was investigated. Uninephrectomy and the injection of adriamycin induced the rat model of glomerulosclerosis. Benazepril (6 mg/kg), valsantan (20 mg/kg), or benazepril (3 mg/kg) plus valsantan (20 mg/kg) was respectively delivered daily by gavage to the rats in three treatment groups for 12 weeks. Apoptosis was examined by means of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL). Immunohistochemistry was adopted to detect the expression of Fas and FasL. Software of pathological analysis quantitated the levels of Fas and FasL. The results showed that as compared with those in the control group, the kidneys in the model group had more severe glomerulosclerosis, much more apoptotic cells and higher levels of expression of Fas and FasL. The degree of glomerulosclerosis, the number of apoptotic cells and the levels of expression of Fas and FasL were reduced by benazepril and valsartan. The combined use of benazepril and valsartan had the best therapeutic effect. It was concluded that benazepril and valsartan could suppress the excessive apoptosis of kidney cells by lowering the expression of the apoptosis-related proteins Fas and FasL, so as to postpone the process of glomerulosclerosis. The combined use of benazepril and valsartan has better therapeutic effect.

Effect of mycophenolate mofetil plus adriamycin on HepG-2 cells

AIM:To investigate the influence of mycophenolate mofetil(MMF)plus adriamycin(ADM)on hepatocellular carcinoma(HCC)cells. METHODS:HCC cells were treated with 100μg/ml of MMF alone(MMF group),1μg/mL of adriamycin(ADM group)alone,or a combination of the drugs(MMF+ ADM group).We performed an 3-[4,5-dimethylthiazol2-yl]-2,5-diphenyl tetrazolium bromide(MTT)assay to measure the growth inhibition rate of HCC cells.Flow cytometry was used to determine the percentage of cells in different phases of the cell cycle and the number of apoptotic cells.Hoechst 33258 staining revealed the morphological changes associated with apoptosis in HCC cells. RESULTS:The results of MTT assays revealed that monotherapy with ADM or MMF showed inhibition of cell growth,while MMF+ADM therapy afforded an inhibition rate of more than 90%with cell distribution in G1 and G2/M phase greater than that in S phase. MMF+ADM treatment also downregulated Bcl-2 expression markedly.The growth of HCC cells was markedly inhibited and apoptosis was enhanced in all the 3 groups.Compared with other 2 groups,the MMF +ADM group showed more obvious apoptosis of cells. CONCLUSION:The MMF plus ADM combination exerts remarkable inhibitory effects on the growth of HCC cells.

Adriamycin induces H2AX phosphorylation in human spermatozoa

Aim： To investigate whether adriamycin induces DNA damage and the formation of γH2AX （the phosphorylated form of histone H2AX） foci in mature spermatozoa. Methods： Human spermatozoa were treated with adriamycin at different concentrations, γH2AX was analyzed by immunofluorescent staining and flow cytometry and doublestrand breaks （DSB） were detected by the comet assay. Results： The neutral comet assay revealed that the treatment with adriamycin at 2 μg/mL for different times （0.5, 2, 8 and 24 h）, or for 8 h at different concentrations （0,4, 2 and 10 μg/mL）, induced significant DSB in spermatozoa. Immunofluorent staining and flow cytometry showed that the expression of γH2AX was increased in a dose-dependent and time-dependant manner after the treatment of adriamycin. Adriamycin also induced the concurrent appearance of DNA maintenance/repair proteins RAD50 and 53BP 1 with γH2AX in spermatozoa. Wortmannin, an inhibitor of the phosphatidylinositol 3-kinase （PI3K） family, abolished the co-appearance of these two proteins with γH2AX. Conclusion： Human mature spermatozoa have the same response to DSB-induced H2AX phosphorylation and subsequent recruitment of DNA maintenance/ repair proteins as somatic cells.

A Modified Method for Preparation of Adriamycin Carried by Magnetic Albumin Microspheres

The targeting of antineoplastic agents to restricted anatomic sites and specific target cells have been challenged clinicians all the time in cancer chemotherapy, which resulted in recent efforts to focus the effects of existing antitumor agents and treatments on tumor cells and spare their effects on normal cells. The drug-carrier complex, adriamycin carried by magnetic albumin microspheres (ADM-MAM) was prepared by using our discovered new and modified method. The physical feature of the prepared drug-carrier microspheres was much better than by the traditional method in comparison. The successful preparation of the drug-carrier complex, ADM-MAM, is one of the key steps for our later further researches in the targeted chemotherapy.

The expression of TRAIL and its receptors in osteosarcoma cells and the apoptosis effect of a combination of TRAIL, adriamycin and IFN-γ on MG-63 cells

Objective： This study investigated the effects of rh-TRAIL with or without chemotherapeutic drugs on the apoptosis of the osteosarcoma cell line, MG-63, and the influence of chemotherapeutic drugs on changes in the expression of DR5 and YinYang 1 （YY1） in MG- 63 cells. Methods： The effects of treatment with rh-TRAIL alone and/or chemotherapetic drugs on MG-63 cell growth inhibition and apoptosis were measured using the MTT assay, FACS analysis ofAunexin V labeled cells, and the mRNA changes of DR5 and YY1 were detected by RT-PCR. Results： Rh-TRAIL protein inhibited the growth of MG-63 cells, and this inhibition was increased by adriamycin and IFN-γ. Adriamycin and IFN-γ significantly facilitated the induction of the expression of DR5 and reduced the expression of YY1. Conclusion： The apoptosis-inducing effect of rh-TRAIL in MG-63 cells was enhanced by chemotherapeutic drugs.

Enhanced antitumor efficacy on hepatoma-bearing rats with adriamycin-loaded nanoparticles administered into hepatic artery

AIM: To investigate the antitumor activity of adriamycin (ADR) encapsulated in nanoparticles (NADR) and injected into the hepatic artery of hepatoma-bearing rats.METHODS: NADR was prepared by the interfacial polymerization method. Walker-256 carcinosarcomas were surgically implanted into the left liver lobes of 60 male Wistar rats, which were divided into 4 groups at random (15 rats per group). On the 7th day after implantation, normal saline (NS), free ADR (FADR), NADR, or ADR mixed with unloaded nanoparticles (ADR+NP) was respectively injected via the hepatic artery (i.a.) of rats in different groups. The dose of ADR in each formulation was 2.0 mg/kg body weight and the concentration was 1.0 mg/mL. Survival time, tumor enlargement ratio, and tumor necrosis degree were compared between each group.RESULTS: Compared with the rats that received NS i.a.,the rats that received FADR or ADR+NP acquired apparent inhibition on tumor growth, as well as prolonged their life span. Further significant anticancer efficacy was observed in rats that received i.a. administration of NADR. Statistics indicated that NADR brought on a more significant tumor inhibition and more extensive tumor necrosis, as compared to FADR or ADR+NP. The mean tumor enlargement ratio on the 7th day after NADR i.a. was 1.106. The mean tumorbearing survival time was 39.50 days. Prolonged life span ratio was 109.22% as compared with rats that accepted NS.CONCLUSION: Therapeutic effect of ADR on liver malignancy can be significantly enhanced by its nanopaticle formulation and administration via hepatic artery.

Ursolic Acid Attenuates Renal Injury Induced by Adriamycin in Mice

Objective: To explore the protective effects of ursolic acid (UA) on adriamycin nephropathy in mice. Methods: Totally 40 male Balb/c mice were randomly divided into normal group, model group, low dose of UA group and high dose of UA group. One-time injection of Adriamycin (ADR) at 10.0 mg/kg via tail vein was used to establish the model. Different doses of UA were administered to the mice in treatment groups from the first day after successful modeling. After 3 consecutive weeks, 24 h urine protein was measured, and BUN, Scr and TG as well as SOD, MDA and GSH were also measured. The IL-1β, TNF-α and TGF-β1 were measured by ELISA;SMAD2/3 phosphorylation and its target protein α-SMA expression were measured by Western Blot;pathological changes of renal tissues were observed. Results: Compared with the model group, UA can significantly reduce the urine protein, BUN, Scr, TG, MDA, IL-1β, TNF-α, TGF-β and SMAD2/3 phosphorylation and its target protein α-SMA expression while increasing the GSH and SOD, and the difference is significant (P Conclusions: Ursolic acid can protect against renal damage by inhibiting oxidative stress and reducing the release of inflammatory cytokines, which may be related to the inhibition of TGF-β1/Smads-related signaling pathway.