• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4807-4814
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• 2012

Purpose: The chemoresistance of human hepatocellular carcinoma (HCC) to cytotoxic drugs, especially intrinsic or acquired multidrug resistance (MDR), still remains a major challenge in the management of HCC. In the present study, possible mechanisms involved in MDR of HCC were identified using a 5-fluorouracil (5-FU)-resistant human HCC cell line. Methods: BEL-7402/5-FU cells were established through continuous culturing parental BEL-7402 cells, imitating the pattern of chemotherapy clinically. Growth curves and chemosensitivity to cytotoxic drugs were determined by MTT assay. Doubling times, colony formation and adherence rates were calculated after cell counting. Morphological alteration, karyotype morphology, and untrastructure were assessed under optical and electron microscopes. The distribution in the cell cycle and drug efflux pump activity were measured by flow cytometry. Furthermore, expression of potential genes involved in MDR of BEL-7402/5-FU cells were detected by immunocytochemistry. Results: Compared to its parental cells, BEL-7402/5-FU cells had a prolonged doubling time, a lower mitotic index, colony efficiency and adhesive ability, and a decreased drug efflux pump activity. The resistant cells tended to grow in clusters and apparent changes of ultrastructures occurred. BEL-7402/5-FU cells presented with an increased proportion in S and G2/M phases with a concomitant decrease in G0/G1 phase. The MDR phenotype of BEL-7402/5-FU might be partly attributed to increased drug efflux pump activity via multidrug resistance protein 1 (MRP1), overexpression of thymidylate synthase (TS), resistance to apoptosis by augmentation of the Bcl-xl/Bax ratio, and intracellular adhesion medicated by E-cadherin (E-cad). P-glycoprotein (P-gp) might play a limited role in the MDR of BEL-7402/5-FU. Conclusion: Increased activity or expression of MRP1, Bcl-xl, TS, and E-cad appear to be involved in the MDR mechanism of BEL-7402/5-FU.

• The Korean Journal of Physiology and Pharmacology
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• 제22권5호
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• pp.513-523
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• 2018

The tumor microenvironment greatly influences cancer cell characteristics, and acidic extracellular pH has been implicated as an essential factor in tumor malignancy and the induction of drug resistance. Here, we examined the characteristics of gastric carcinoma (GC) cells under conditions of extracellular acidity and attempted to identify a means of enhancing treatment efficacy. Acidic conditions caused several changes in GC cells adversely affecting chemotherapeutic treatment. Extracellular acidity did inhibit GC cell growth by inducing cell cycle arrest, but did not induce cell death at pH values down to 6.2, which was consistent with down-regulated cyclin D1 and up-regulated p21 mRNA expression. Additionally, an acidic environment altered the expression of atg5, HSPA1B, collagen XIII, collagen XXAI, slug, snail, and zeb1 genes which are related to regulation of cell resistance to cytotoxicity and malignancy, and as expected, resulted in increased resistance of cells to multiple chemotherapeutic drugs including etoposide, doxorubicin, daunorubicin, cisplatin, oxaliplatin and 5-FU. Interestingly, however, acidic environment dramatically sensitized GC cells to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Consistently, the acidity at pH 6.5 increased mRNA levels of DR4 and DR5 genes, and also elevated protein expression of both death receptors as detected by immunoblotting. Gene silencing analysis showed that of these two receptors, the major role in this effect was played by DR5. Therefore, these results suggest that extracellular acidity can sensitize TRAIL-mediated apoptosis at least partially via DR5 in GCs while it confers resistance to various type of chemotherapeutic drugs.

• 한국동물위생학회지
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• 제46권3호
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• pp.211-218
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• 2023

This study was carried out to investigate the prevalence and antimicrobial resistance of Salmonella serotypes in duck farms of Jeollanam-do Province, South Korea. A total of 1112 samples (breeder ducks, 286; broiler ducks, 826) were collected from 196 duck farms (breeder duck farms, 25; broiler duck farms, 171) between January 2018 and November 2019. The total prevalence of Salmonella serotypes was 45.4% (89/196) in the duck farms, with no significant difference between prevalence in breeder and broiler duck farms (48% and 45%, respectively; P>0.05). The most prevalent serotype among the 127 Salmonella isolates was Salmonella Typhimurium (20.5%) followed by Salmonella Albany (17.3%), Salmonella Hadar (15.7%), and Salmonella Enteritidis (11.8%). Maximum resistance was observed against penicillin (78.74%), followed by tetracycline (68.50%), and kanamycin (65.35%). Of the 127 isolates, 117 (92.13%) were resistant to ≥3 antimicrobials and 2 to all 18 antimicrobials. Our results demonstrate the presence of Salmonella strains and their resistance to multiple antimicrobials, thus indicating a public health concern in South Korea. The emergence of Salmonella stains that are resistant to multiple drugs highlight the need for careful use of antimicrobials in duck farms.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제15권2호
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• pp.63-73
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• 2012

Development of antiviral resistance to lamivudine is the most important factor for the treatment failure. It is necessary to establish proper guidelines to overcome drug resistance for children with chronic hepatitis B. Primary treatment with lamivudine should be considered if patients are in immune-clearance phase and have persistently elevated ALT levels more than twice the upper limit of normal value. Before initiating the therapy, careful consideration of the patient's status is required to exclude abnormal liver function tests due to other causes. The treatment option should be carefully decided to suppress the viral replication effectively. To obtain good compliance, clinicians should educate patients and their parents. Appropriate monitoring for virologic breakthrough and genotypic resistance is important in deciding to change the treatment plan. Sequential monotherapy should be avoided and a combination of drugs in other categories is recommended. New antiviral agents, such as entecavir and tenofovir, which have high potency and high genetic barrier, are soon expected to be available for use with children.

• Natural Product Sciences
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• 제1권1호
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• pp.50-54
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• 1995

Staphylococcus aureus SA2, which was isolated from patient, is resistant to 10 usual antibiotics. The methanolic extracts of 21 well-known herb materials were combined with 10 antibiotics and applied to cheek inhibitory effects on the resistance of S. aureus SA2. The hexane fractions from methanolic extracts of Acori graminei Rhizoma and Anethi Fructus had most potent activity to inhibit the resistance of the bacteria when combined with ampicilin or chloramphenicol.

• Mycobiology
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• 제45권4호
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• pp.426-429
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• 2017

A yeast-like organism was isolated from a urine sample of a 6-year-old neutered male miniature poodle dog with urinary tract infection, diabetes ketoacidosis, and acute pancreatitis. We identified the yeast-like organism to be Candida glabrata and found that this fungus was highly resistant to azole antifungal drugs. To understand the mechanism of azole resistance in this isolate, the sequences and expression levels of the genes involved in drug resistance were analyzed. The results of our analysis showed that increased drug efflux, mediated by overexpression of ATP transporter genes CDR1 and PDH1, is the main cause of azole resistance of the C. glabrata isolated here.

• BMB Reports
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• 제56권6호
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• pp.326-334
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• 2023

Antibiotic resistance (AR) is a silent pandemic that kills millions worldwide. Although the development of new therapeutic agents against antibiotic resistance is in urgent demand, this has presented a great challenge, especially for Gram-negative bacteria that have inherent drug-resistance mediated by impermeable outer membranes and multidrug efflux pumps that actively extrude various drugs from the bacteria. For the last two decades, multidrug efflux pumps, including AcrAB-TolC, the most clinically important efflux pump in Gram-negative bacteria, have drawn great attention as strategic targets for re-sensitizing bacteria to the existing antibiotics. This article aims to provide a concise overview of the AcrAB-TolC operational mechanism, reviewing its architecture and substrate specificity, as well as the recent development of AcrAB-TolC inhibitors.

• Natural Product Sciences
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• 제20권1호
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• pp.1-6
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• 2014

P-glycoprotein (P-gp) is a permeability glycoprotein also known as multidrug resistance protein 1 (MDR1). P-gp is an ATP-binding cassette (ABC) transporter that pumps various types of drugs out of cells. These transporters reduce the intracellular concentrations of drugs and disturb drug absorption. The Caco-2 cell permeability assay system is an effective in vitro system that predicts the intestinal absorption of drugs and the functions of enzymes and transporters. Rhodamine-123 (R-123) and digoxin are well-known P-gp substrates that have been used to determine the function of P-gp. Efflux of P-gp substrates by P-gp has been routinely evaluated. To date, a number of herbal medicines have been tested with Caco-2 cell permeability assay system to assess bioavailability. There are growing efforts to find phytochemicals that potentially regulate P-gp function. The Caco-2 cell permeability assay system is a primary strategy to search for candidates of P-gp inhibitors. In this mini review, we have summarized the P-gp modulation by herbal extracts, decoctions or single components from natural products using Caco-2 cell permeability assays. Many natural products are known to regulate P-gp and herbal medicines could be used in combination with conventional drugs to enhance bioavailability.

• 한국컴퓨터정보학회논문지
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• 제21권7호
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• pp.61-66
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• 2016

The frequency of obesity has risen dramatically in recent years but only few safe and effective drugs are currently available. In addition, obesity can induce type 2 diabetes (T2DM), hyperlipidemia and fatty liver disease. Recently, protective effect of purslane extract (PE) on obesity has been reported, but little is known about the role and mechanism of PE in obesity. This study aimed to evaluate the effect of PE on obesity and diabetes in obese mice. In addition, the effect of PE was compared with anti-obesity and diabetes drugs. High-fat diet (HFD)-induced obese mice were treated for 8 weeks with drugs as follows: PE, orlistat, metformin, voglibose or pioglitazone. While PE mixed with normal diet did not have any effects on BW in non-obese mice, PE mixed with HFD significantly reduced BW gain, insulin resistance, and glucose intolerance, without affecting food intake and appetite in obese mice. The effect was comparable to the effects of anti-obesity and diabetes drugs. Furthermore, PE significantly increased the activity of hepatocellular anti-oxidant enzymes, leading to protection of liver from oxidative stress in obese mice. These results suggest that PE treatment may be a useful tool for preventing obesity and complication of obesity.

• 대한의생명과학회지
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• 제25권2호
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• pp.159-169
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• 2019

Breast cancer stem cells (BCSCs) in breast cancer cells have self-renewal ability and differentiation potential. They are also resistant to drugs after chemotherapy. To overcome this resistance, we designed negatively charged 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG)-based liposomes for drug delivery. These liposomes have enhanced the therapeutic effects of a range of antitumor therapies by increasing the cellular uptake and improving drug delivery to targets sites. In this study, we investigated whether DMPG-POPC liposomes, including the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC), can specifically bind to MCF-7 breast cancer cells and increase cellular uptake compared with that by CHOL-POPC liposomes. We also estimated the cytotoxicity of DMPG-POPC liposomes encapsulated with both metformin (Met) and sodium salicylate (Sod) against breast cancer cells and BCSCs compared with that of the free drugs. Our results demonstrated that these dual drug-encapsulated liposomes significantly enhanced the cytotoxic and anti-colony formation abilities compared with individual drug-encapsulated liposomes or free drugs in BCSCs. Overall, our results suggest that DMPG-POPC liposomes containing two drugs (Met + Sod) show promise for synergistic anti-cancer therapy of breast cancer by increasing drug delivery efficiency into breast cancer cells and BCSCs.