Incidence, risk factors and clinical outcome of multidrug-resistant organisms after heart transplantation

BACKGROUND Transplant recipients commonly harbor multidrug-resistant organisms(MDROs),as a result of frequent hospital admissions and increased exposure to antimi-crobials and invasive procedures.AIM To investigate the impact of patient demographic and clinical characteristics on MDRO acquisition,as well as the impact of MDRO acquisition on intensive care unit(ICU)and hospital length of stay,and on ICU mortality and 1-year mortality post heart transplantation.METHODS This retrospective cohort study analyzed 98 consecutive heart transplant patients over a ten-year period(2013-2022)in a single transplantation center.Data was collected regarding MDROs commonly encountered in critical care.RESULTS Among the 98 transplanted patients(70%male),about a third(32%)acquired or already harbored MDROs upon transplantation(MDRO group),while two thirds did not(MDRO-free group).The prevalent MDROs were Acinetobacter baumannii(14%),Pseudomonas aeruginosa(12%)and Klebsiella pneumoniae(11%).Compared to MDRO-free patients,the MDRO group was characterized by higher body mass index(P=0.002),higher rates of renal failure(P=0.017),primary graft dysfunction(10%vs 4.5%,P=0.001),surgical re-exploration(34%vs 14%,P=0.017),mechanical circulatory support(47%vs 26%P=0.037)and renal replacement therapy(28%vs 9%,P=0.014),as well as longer extracorporeal circulation time(median 210 vs 161 min,P=0.003).The median length of stay was longer in the MDRO group,namely ICU stay was 16 vs 9 d in the MDRO-free group(P=0.001),and hospital stay was 38 vs 28 d(P=0.006),while 1-year mortality was higher(28%vs 7.6%,log-rank-χ2:7.34).CONCLUSION Following heart transplantation,a predominance of Gram-negative MDROs was noted.MDRO acquisition was associated with higher complication rates,prolonged ICU and total hospital stay,and higher post-transplantation mortality.

Reversal of Multi-Drug Resistance by Vector-Based-ShRNA-Mdr1 In Vitro and In Vivo

In order to investigate the effects of vector-based hairpin small interference RNA （shRNA） on the reversal of multi-drug resistance （mdr） of A2780/Taxol cells, a novel vector pEGFP-HI/mdrl containing mdrl-shRNA targeting at position 2943-2963 of mdrl was designed and synthesized. Subsequently, A2780/Taxol cells were transfected with pEGFP-H1/rndrl, and the expression ofmdrl mRNA and P-gp was detected by using RT-PCR and Western blot respectively. MTT was used to measure the 50% inhibition concentration （IC50） of Taxol to A2780/Taxol cells. The results showed that at the 24th and 48th h after transfection, the expression of mdrl mRNA was decreased to （52.1±1.0）% and （0.01±1.7）%, and that of P-gp decreased to （88.3±2.1）% and 0%, respectively. At the 48th h after transfection, the relative reversal rate of A2780/Taxol cells to Taxol was 69.54%. In vivo, the nude mice xenografts were injected with pEGFP-H1/mdrl, and then administrated Taxol. The tumor volume in pEGFP-H1/mdrl-transfected group was significantly reduced as compared with that in blank control group or pEGFP-Hl-transfected group （807.20±103.16 vs 1563.78±210.54 or 1480.78±241.24 mm^3, both P〈0.01）. These results suggested that transfection of pEGFP-HI/mdrl could efficiently down-regulate the expression of mdrl mRNA and P-gp in A2780/Taxol cells, and effectively restore the sensitivity of A2780/Taxol ceils to Taxol both in vitro and in vivo.

In-vitro antimicrobial activity of marine actinobacteria against multidrug resistance Staphylococcus aureus

Objective:To investigate the antibacterial aclivily of marine actinobacteria against multidrug resistance Staphylococcus aureus(MDRSA).Methods:Fifty one actinobacterial strains were isolated from salt pans soil,costal area in Kothapattanam,Ongole,Andhra Pradesh.Primary screening was done using cross-streak method against MDRSA.The bioaclive compounds are extracted from efficient actinobacteria using solvent extraction.The antimicrobial activity of crude and solvent extracts was perfomied using Kirby-Bauer method.MIC for ethyl acetate extract was determined by modified agar well diffusion method.The potent actinobacteria are identified using Nonomura key,Shirling and Gottlieb 1966 with Bergey's manual of determinative bacteriology.Results:Among the fifty one isolates screened for antibacterial activity,SRB25were found efficient against MDRSA.The ethyl acetate extracts showed high inhibition against test organism.MIC test was performed with the ethyl acetate extract against MDRSA and found to be 1 000μg/mL.The isolaled actinobacteria are identified as Streptomyces sp with the help of Nonomura key.Conclusions:The current investigation reveals that the marine actinobacteria from salt pan environment can be able to produce new drug molecules against drug resistant microorganisms.

Relationship between Methylation Status of Multi-drug Resistance Protein(MRP) and Multi-drug Resistance in Lung Cancer Cell Lines

Objective： To study the relationship between the methylation status of multi-drug resistance protein （MRP） gene and the expression of its mRNA and protein in lung cancer cell lines. Methods： Human embryo lung cell line WI-38, lung adenocarcinoma cell line SPCA-1 and its drug-resistant cells induced by different concentrations of doxorubicin were treated with restriction endonuclease Eco47III. The methylation status of MRP was examined by PCR, and the expressions of its mRNA and protein were evaluated by in situ hybridization and immunohistochemistry. Results： MRP gene promoter region of WI-38 cells was in hypermethylation status, but the promoter region of MRP in SPCA-1 cells and their resistant derivatives induced by different concentrations of doxorubicin were in hypomethylation status. There were significant differences in the expression of MRP mRNA among WI-38 cell line, SPCA-1 cells and their drug-resistant derivatives induced by different concentration of doxorubicin. Consistently, MRP immunostaining presented similar significant differences. Conclusion： The promoter region of MRP in SPCA-1 lung adenocarcinoma cells was in hypomethylation status. The hypomethylation status of 5＇ regulatory region of MRP promoter is an important structural basis that can increase the activity of transcription and results in the development of drug resistance in lung cancer.

The Roles of Four Multi-drug Resistance Proteins in Hepatocellular Carcinoma Multidrug Resistance

The roles of multi-drug resistance protein 1 （MDR1）, multi-drug resistance related protein 1 （MRP1）, lung resistance protein （LRP） and breast cancer resistance protein （BCRP） in the multi-drug resistance （MDR） of hepatocellular carcinoma （HCC） were studied. By exposing HepG2 cell line to progressively increased concentrations of adriamycin （ADM）, HepG2 multi-drug resistant subline （HepG2/ADM） was induced. The MDR index of HepG2/ADM was detected by using MTT. The expressions of the four MDR proteins in the three cell lines （L02, HepG2, HepG2/ADM） were investigated at mRNA and protein levels by real-time RT-PCR and Western blot respectively. Our results showed that when the ADM concentration was under 100 pg/L, HepG2 could easily be induced to be drug-resistant. The IC50 of the HepG2/ADM to ADM was 282 times that of HepG2. The expression of MDR1 and BCRP mRNA in HepG2/ADM cells were 400 and 9 times that of HepG2 cells respectively while there was no difference in the mRNA expressions of MRPl and LRE There was no difference between HepG2 and L02 cells in the mRNA expressions of the four genes. At the protein level, the expressions of MDRI, BCRP and LRP but MRPl in HepG2/ADM were significantly higher than those of HepG2 and L02. Between HepG2 and L02, there was no difference in the expressions of four genes at the protein level. HepG2/ADM is a good model for the study of MDR. The four genes are probably the normally expressed gene in liver. The expressions of MDRl and BCRP could be up-regulated by anti-cancer agents in vitro. The MDR of HCC was mainly due to the up-regulation of MDR1 and BCRP but MRP1 and LRE These findings suggest they may serve as targets for the reversal of MDR of HCC.

β-escin reverses multidrug resistance through inhibition of the GSK3β/β-catenin pathway in cholangiocarcinoma

AIM: To develop a safe and effective agent for cholangiocarcinoma(CCA) chemotherapy. METHODS: A drug combination experiment was conducted to determine the effects of β-escin in c o m b i n a t i o n w i t h c h e m o t h e ra p y o n C C A c e l l s. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was performed to determine the effects of β-escin and common chemotherapeutics on the proliferation of human CCA cells(QBC939, Sk-Ch A-1, and MZ-Ch A-1). Immunocytochemistry was used to detect the expression of P-glycoprotein(P-gp) protein. Luciferase reporter assay was used to detect the activation of the Wnt/β-catenin pathway. The protein levels of P-gp, p S9-GSK3β, p T216-GSK3β, GSK3β, β-catenin, and p-β-catenin were further confirmed by western blotting.RESULTS: The drug sensitivity of QBC939 and QBC939/5-fluorouracil(5-FU) cells to 5-FU, vincristine sulfate(VCR), or mitomycin C was significantly enhanced by β-escin compared with either agent alone(P < 0.05). In addition, the combination of β-escin(20 μmol/L) with 5-FU and VCR was synergic with a combination index < 1. Further investigation found that the m RNA and protein expression of P-gp was downregulated by β-escin. Moreover, β-escin induced GSK3β phosphorylation at Tyr-216 and dephosphorylation at Ser-9, resulting in phosphorylation and degradation of β-catenin. Interestingly, activation of the GSK3β/β-catenin pathway induced by Wnt3 a resulted in upregulation of P-gp, which was effectively abolished by β-escin, indicating that β-escin down-regulated P-gp expression in a GSK3β-dependent manner.CONCLUSION: β-escin was a potent reverser of P-gpdependent multidrug resistance, with said effect likely being achieved via inhibition of the GSK3β/β-catenin pathway and thus suggesting a promising strategy of developing combination drugs for CCA.

Drug Resistance Pattern in Pulmonary Tuberculosis Patients and Risk Factors Associated with Multi-Drug Resistant Tuberculosis

Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its associated cost and side effects. The objective of this study was to assess the drug resistance pattern and assess risk factor associated with MDR-TB among pulmonary tuberculosis patients attending National Tuberculosis Center. Methodology: The comparative cross sectional study was conducted at National Tuberculosis Center during August 2015 to February 2015. Early morning sputum samples were collected from pulmonary tuberculosis suspected patients and subjected to Ziehl-Neelsen staining and fluorochrome staining and culture on Lowenstein-Jensen (LJ) medium. Drug Susceptibility test was performed on culture positive isolates by using proportion method. Univariate and multivariate analysis was computed to assess the risk factors of MDR-TB. Results: Out of 223 sputum samples, 105 were fluorochrome staining positive, 85 were ZN staining positive and 102 were culture positive. Out of 102 culture positive isolates, 37.2% were resistance to any four anti-TB drugs. 11 (28.9%) were initial drug resistance and 28 (43.7%) were acquired drug resistance. The overall prevalence of MDR-TB was 11.7%, of which 2 (5.3%) were initial MDR-TB and 10 (15.6%) were acquired MDR-TB. Univariate and multivariate analysis showed female were significantly associated (P = 0.05) with MDR-TB. Conclusion: Drug resistance TB particularly MDR-TB is high. The most common resistance pattern observed in this study was resistance to both isoniazid and rifampicin. Female were found to be associated with MDR-TB. Thus, early diagnosis of TB and provision of culture and DST are crucial in order to combat the threat of DR-TB.

Diagnostic and therapeutic progress of multi-drug resistance with anti-HBV nucleos(t)ide analogues

Nucleos(t)ide analogues(NA) are a breakthrough in the treatment and management of chronic hepatitis B.NA could suppress the replication of hepatitis B virus(HBV) and control the progression of the disease.However,drug resistance caused by their long-term use becomes a practical problem,which influences the long-term outcomes in patients.Liver transplantation is the only choice for patients with HBV-related end-stage liver disease.But,the recurrence of HBV after transplantation often caused by the development of drug resistance leads to unfavorable outcomes for the recipients.Recently,the multi-drug resistance(MDR) has become a common issue raised due to the development and clinical application of a variety of NA.This may complicate the antiviral therapy and bring poorly prognostic outcomes.Although clinical evidence has suggested that combination therapy with different NA could effectively reduce the viral load in patients with MDR,the advent of new antiviral agents with high potency and high genetic barrier to resistance brings hope to antiviral therapy.The future of HBV researches relies on how toprevent the MDR occurrence and develop reasonable and effective treatment strategies.This review focuses on the diagnostic and therapeutic progress in MDR caused by the anti-HBV NA and describes some new research progress in this field.

Multi-Drug Resistance Pattern of Lactose Non-Fermenting <i>Escherichia coli</i>as Causative Agent of Urine Tract Infections in Luanda, Angola

This prospective study was carried out to assess the sensitivity and resistance pattern of lactose non-fermenting Escherichia coli from July 2018 to December 2018 in the Laboratory of Microbiology at Luanda Medical Center, Angola. Out of 1170 patient, a total of 120 urine specimens infected with Escherichia coli (>105 CFU/ml) were collected according to the routine protocol of urinalysis. Among these 120 isolates, 25 (21%) isolates were determined as “atypical”, lactose non-fermenting E. colis trains. The twenty-five lactose non-fermenting Escherichia coli strains isolated from urine samples in Luanda Medical Center were declared as Multiple Drugs-Resistant strains with high resistance to Cefalexine (100%), Cefuroxime (100%), Ceftriaxone (92%), Gentamycin (92%), Ciprofloxacin (72%) and Amoxiciclin/Clavulanic (80%). The alarming resistance level to the first-choice drugs for the treatment of urinary tract infections caused by non-fermentative lactose E. coli was observed.

Expression and Prognostic Significance of Multidrug Resistance Associated Protein (MRP) Gene in Non-small Cell Lung Cancer by in Site Hybridization

Objective: To study on the effect of MRP gene overexpression on prognosis of patients with non-small lung cancer (NSCLC). Methods: Paraffin-embedded tissues from 47 cases of NSCLC who had undergone radical tumor resection were examined for expression of MRP gene mRNA by in situ hybridization using labelled digoxigenin probes combined with immunohistochemistry. All the patients were retrospectively followed-up. Results: All of the 47 lung cancer specimens were found to have overexpression of MRP gene mRNA. It was significantly correlated with patients' survival time, response to chemotherapy, recurrence or metastases after surgery, but was not correlated with histology, tumor size, node status, TNM stage, degree of differentiation, age and sex. Conclusion: Overexpression of MRP gene is a marker of prognostic significance in patients with NSCLC.

Reversal of HCC Drug Resistance by Using Hammerhead Ribozymes against Multidrug Resistance 1 Gene

To reverse multidrug resistance（MDR） of HepG2 by anti-MDR1 hammerhead ribozyme, an anti-MDR1 hammerhead ribozyme was developed and delivered to P-gp-overproducing human hepatocarcinoma cell line HepG2 by a retroviral vector containing RNA polymerase Ⅲ promoter. The expression of mdrl/Pgp and Rz was detected in HepG2, HepG2 muhidrug-resistant cell line and HepG2 Rz-transfected cells by semi-quantitative RT-PCR and Western blot methods. Moreover, MTT assay was employed to detect the sensitivity of these ribozyme-transfected cells, and Rhodamine123 （Rh123） was used to test the function of Pgp. The Rz- transfected HepG2 cells became doxorubicin-sensitive, which was concomitant with the decreased MDR1 expression. The study showed that the retrovirus vector encoding the anti-MDR1 ribozyme may be applicable to the treatment of MDR cells.

Direct and Residual Microbicidal Efficacy of Various Antiseptics against Multi-Drug Resistant Bacteria

Background: Infections in ICU’s patients are known to often originate from the colonization of wounds by the patient’s endogenous microbiota, and to eventually lead to secondary sepsis. Aim: to compare in vitro the direct and residual effects after different exposure times of 4% chlorhexidine, and of 0.1% and 0.04% polyhexanide (in gel and solution forms), on ATCC-microorganisms, and too, on bacterial strains obtained from ICU patients. Methods: We used wild multi-drug resistant strains recently obtained from the wounds of patients hospitalized at ICU and reference strains from the American Type Culture Collection (ATCC). Chlorhexidine 4% was studied as a reference solution. The direct and residual effects of the 0.1% and 0.04% polyhexanide, in gel and solution forms, were analyzed using cotton germ carriers. To evaluate the direct effect, we exposed the strains to the antiseptic. To assess the residual effect, the germ-carriers were impregnated with antiseptic and were allowed to dry before we contaminated them. We inoculated the germ carriers in a culture medium with an inhibitor of antiseptic effect to count the number of surviving microorganisms. Findings: 0.1% Polyhexanide solution proved a direct and residual efficacy after 24 hours equivalent to 4% chlorhexidine. Is very important to highlight that this great efficacy did not change according to whether they were ATCC or multidrug-resistant strains. Conclusions: 0.1% polyhexanide demonstrated a great direct and residual efficacy (like 4% chlorhexidine), against multi-drug resistant strains isolated from ICU’s patients. Moreover, due to its few cytotoxicity against keratinocytes and fibroblasts can be an optimal antiseptic for burns, wounds or ulcers.

Molecular characterization of antimicrobial multi-drug resistance in non-typhoidal Salmonellae from chicken and clam in Mangalore, India

Salmonella enterica has been documented as one of the leading causes of salmonellosis throughout the world and is most commonly associated with the consumption of contaminated food products. Thus, this research was aimed at studying the antimicrobial susceptibility pattern and detection of quinolone resistance in Salmonella spp isolated from food of animal origin. Thirty-six Salmonella isolates comprising 8 from poultry and 28 from seafood（clams） were identified, serotyped and characterized for their antimicrobial susceptibility against 10 different antibiotics. Plasmid DNA was isolated from all the isolates by alkaline lysis, quinolone resistant non-typhoidal S. Weltevreden were examined for mutation in the DNA gyrase coding gene. Among the 36 Salmonella isolates, 20 were S. weltevreden（8 from poultry and 12 from seafood） and 16 were S. Typhimurium（from seafood）. All the isolates showed multiple resistance to nalidixic acid, tetracycline, co-trimoxazole and nitrofurantoin, but, interestingly, the isolates were 100% susceptible to ampicillin, chloramphenicol and gentamicin. Resistant isolates from the study carried the genes responsible for resistance to respective antibiotics. The strain S130 isolated in the study showed single point mutation,Asp87Gly, at position 87 in quinolone resistance determining region. It revealed mutation in quinolone resistance determining region as a cause for quinolone resistance in non-typhoidal Salmonellae. The occurrence of genes accountable for plasmid mediated resistance to quinolones（viz., qnrA, qnrB and qnrS） in plasmid of non-typhoidal Salmonellae isolates provides evidence for plasmid mediated quinolone resistance.

Multi Drug Resistance Bacterial Isolates of Surgical Site Infection

Multi drug resistance microorganism is considered to be one of the major health problems. The aim of this study was to determine antibiotic susceptibility pattern of bacterial pathogens of surgical site infection. A total 250 samples were included, out of which 62.4% showed significant bacterial growth. Gram negative bacteria were 85.25% and gram positive bacteria were 14.75%;among them 65.38% of the total isolates were multi drug resistance (MDR). The age group between 31 - 40 found the highest number of isolates 22.4%. Among gram negative bacilli, the highest production of MDR was found in Acinetobacter spp. followed by Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli. In gram positive cocci, the highest production of MDR was found in Staphylococcus aureus. Acinetobacter spp. was found highly susceptible to amikacin and gentamycin 20.1% followed by ofloxacin and ciprofloxacin 18.6% and 16.2% respectively. Staphylococcus aureus showed 100% sensitive to clindamycin whereas penicillin showed 100% resistance followed by amoxycillin (93.75%). Amikacine and clindamycin were drugs of choice for gram negative and gram positive bacteria respectively. This study showed that alarming increase of infections was caused by multi drug resistance bacterial organisms. It increases length of stay and may produce lasting sequelae and requires extra resources for investigations, management and nursing care. Surveillance of surgical site infection is a useful tool to demonstrate the magnitude of the problem and find out appropriate preventive methods.

Monitoring and Analysis on Multi Drug Resistance of Escherichia coli from Captive Population Amur Tiger

In order to investigate the multi drug resistance to Escherichia coli from captive population Amur tiger,E. coli strains were isolated from the fecal samples of tiger in Heilongjiang Amur Tiger Park in Harbin. The sensitivity of E. coli isolates to 14 antibiotics was determined by scrip diffusion method. The results indicated that all the isolates varied in drug resistance to different antibiotics; the isolates gave high resistance to ampicillin,with a drug fast rate of 100%; over80% of the isolates were resistant to tetracycline and Paediatric Compound Sulfamethoxazole Tablets(SMZ- TMP),and over 70% of the isolates were sensitive to aztreonam,amoxicillin /potassium clavulanate. Most of the isolates had high sensitive to aztreonam and amoxicillin / clavulanate acid.

Identification, Synthesis, Isolation and Spectral Characterization of Multidrug-Resistant Tuberculosis (MDR-TB) Related Substances

Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.

Molecular characteristics,antibiogram and prevalence of multi-drug resistant Staphylococcus aureus (MDRSA) isolated from milk obtained from culled dairy cows and from cows with acute clinical mastitis

Objectives: To study the molecular characteristics, antibiogram and prevalence of multidrug resistant Staphylococcus aureus(S. aureus)(MDRSA) isolated from milk obtained from culled dairy cows and from cows with acute clinical mastitis.Methods: Bacteria were cultured from 188 quarter milk samples obtained from cows before culling(n=139) and from cows affected with acute mastitis(n=49) belonging to 10 dairy farms. The bacteria were identified using colony moiphology, Gram staining and biochemical characteristics. S. aureus isolates were then subjected to molecular characterization using PCR targeting 16 S rRNA and mecA gene to identify Methicillin resistant S. aureus(MRSA). The antibiogram of all isolates was performed using the Kirby-Bauer disk diffusion method against 10 commonly used antibiotics in dairy farms.Results: S. aureus was isolated from 19(13.7%) samples obtained from culled cows and 11(22.4%) samples obtained from cows with acute mastitis. In both culled cows and cows with acute mastitis, in vitro antibiogram revealed that 100% of S. aureus isolates were resistant to erythromycin, penicillin G, streptomycin, doxycyclin, and trimethoprim/sulpha. The prevalence of MRSA in milk of culled cows and cows with acute mastitis was 26.3% and 18.2%, respectively, with an overall prevalence of 3.7% among all samples. All MRSA isolates were completely resistant to all tested antibiotics. All MRSA isolates were positive for the presence of the mecA gene.Conclusions: MRSA carrying the mecA gene were isolated from mastitic milk from dairy cows in Jordan for the first time. MRSA may pose a potential health risk to the public, farm workers and veterinarians.

Reversion of Multidrug-Resistance by Proteasome Inhibitor Bortezomib in K562/DNR Cell Line

Objective：To observe the reversion of multi-drug resistance by proteasome inhibitor bortezomib in K562/DNR cell line and to analyze the possible mechanism of reversion of multidrug-resistance.Methods：MTT method was used to determine the drug resistance of K562/DNR cells and the cellular toxicity of bortezomib.K562/DNR cells were cultured for 12 hours,24 hours and 36 hours with 100 μg/ml DNR only or plus 4 μg/L bortezomib.The expressions of NF-κB,IκB and P-gp of K562/DNR were detected with Western blot method,the activity of NF-κB was tested by ELISA method and the apoptosis rate was observed in each group respectively.Results：The IC50 of DNR on cells of K562/S and K562/DNR groups were 1.16 μg/ml and 50.43 μg/mL,respectively.The drug-resistant fold was 43.47.The IC10 of PS-341 on Cell strain K562/DNR was 4 μg/L.Therefore,4 μg/L was selected as the concentration for PS-341 to reverse drug-resistance in this study.DNR induced down-regulation of IκB expression,up-regulation of NF-κB and P-gp expression.After treatment with PS-341,a proteasome inhibitor,the IκB degradation was inhibited,IκB expression increased,NF-κB and P-gp expression decreased in a time dependent manner.Compared to DNR group,the NF-κB p65 activity of DNR＋PS-341 group was decreased.Compared to corresponding DNR group,DNR induced apoptosis rate increases after addition of PS-341 in a time dependent manner.Conclusion：Proteasome inhibitor bortezomib can convert the leukemia cell drug resistance.The mechanism may be that bortezomib decreases the degradation of IκB and the expression of NF-κB and P-gp,therefore induces the apoptosis of multi-drug resistant cells.