• BMB Reports
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• 제34권1호
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• pp.66-72
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• 2001

To investigate the mechanism of adriamycin (ADM) resistance in the ADM resistant subline PC-14/ADM, we examined the expressions of p-glycoprotein (P-gp), topoisomerase I (Topo I) and II (Topo II), glutathione-S-transferases (GSTs), tissue transglutaminase (t-TG), epidermal growth factor receptor (EGFR), and E-cadherin and the activity of superoxide dismutase (SOD) in PC-14 and PC-14/ADM cells. There was no change in the cellular levels of P-gp, Topo I, Topo II, and the two isoforms of GSTs. However, SOD activity in PC-14/ADM cells was 2.38 fold higher than that in PC-14 cells. A marked induction of the t-TG expression was also observed in PC-14/ADM cells. In addition to those changes, expressions of EGFR and E-cadherin were down regulated in PC-14/ADM cells. Therefore, molecular modifications such as an increase in SOD activity, induction of the t-TG expression, and down regulation of EGFR and E-cadherin expressions may play important roles in PC-14/ADM cells during the development of ADM resistance.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6757-6760
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• 2013

Gastric cancer is one of the most frequently occurring malignancies in the world. Development of multiple drug resistance (MDR) to chemotherapy is known as the major cause of treatment failure for gastric cancer. Multiple drug resistance 1/P-glycoprotein (MDR1/p-gp) contributes to drug resistance via ATP-dependent drug efflux pumps and is overexpressed in many solid tumors including gastric cancer. To investigate the role of MDR1 knockdown on drug resistance reversal, we knocked down MDR1 expression using shRNA in drug resistant gastric cancer cells and examined the consequences with regard to adriamycin (ADR) accumulation and drug-sensitivity. Two shRNAs efficiently inhibited mRNA and protein expression of MDR1 in SGC7901-MDR1 cells. MDR1 knockdown obviously decreased the ADR accumulation in cells and increased the sensitivity to ADR treatment. Together, our results revealed a crucial role of MDR1 in drug resistance and confirmed that MDR1 knockdown could reverse this phenotype in gastric cancer cells.

• Journal of Nutrition and Health
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• 제33권2호
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• pp.141-146
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• 2000

This study was conducted to investigate the effects of vitamin E supplementation renal lipid peroxidation in high fat diet and adriamycin (ADR) induced experimental nephrotic syndrome model rats. Treated rats were injected intraperitoneally with ADR (2mg/kgBW/wk) once a week for four weeks. control rats were injected with saline solution instead of ADR. The rats in each group were fed experimental diets of three levels of vitamin E for 10 weeks: Normal (501U/kg diet), high (5,000IU/kg diet), excess (7,500IU/kg diet). The high fat diet and ADR treatment was performed to induce the decrease of kidney functions. Serum total cholesterol was significantly decreased by the excess supplementation. But there was no effect of vitamin E supplementation on serum total lipid and triglyceride. Thiobarbituric acid reacting substances(TBARS) was significantly decreased at high and excess supplementation. Glutathione reductase (GR), glutathione peroxidase ({TEX}$GP_{x}${/TEX}) and catalase activities (CAT) were measured as antioxidative enzymes. The renalglutathione reductase (GR) and catalase activities (CAT) were inclined to elevate by vitamin E supplementation. Thus the vitamin E supplementation was found to have an antioxicant effect. These results suggested that vitamin E supplementation could alleviate the changes in renal lipid peroxidation.

• 한국환경성돌연변이발암원학회지
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• 제17권1호
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• pp.7-11
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• 1997

Variations in adriamycin uptake and cytotoxicity were studied in tumor cells that were grown in different growth states and microenvironments. RIF-1 tumor cells were maintained in an RPMI 1640 medium, and grown in either a monolayer or multicell spheroids. For exponentially growing cells, adriamycin cytotoxicity increased with increased dosage up to 2.5 $\mu$g/ml, and this cytotoxicity was reduced when the cells were grown in a plateau phase or in an acidic microenvironment (pH 6.6). This reduced cytotoxicity was correlated with the uptake of the drug. For multicell spheroids, the cytotoxicity of the drug was reduced dramatically, and this reduction was also correlated with a reduced uptake of the drug and an acidic pH inside of the spheroids. When the drug cytotoxicity was evaluated at different locations within the spheroids, the cells in the inner regions were least affected by the drug, suggesting that both an acidic microenvironment and noncycling plateau phase cells are contributing factors in decreasing the efficacy of the drug in an organized tissue, such as multicell spheroids.

• Journal of Yeungnam Medical Science
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• 제6권2호
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• pp.195-205
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• 1989

암의 화학요법에 있어서 내성생성으로 인한 치료의 장애가 암 치료 실패의 중요 원인이 되며, 분 연구는 암세포의 항암제에 대한 내성 생성에 대한 특성을 연구 보고하였다. 사람의 위암 세포주 SNU-1에 대한 내성 유발을 위하여 세포배양액에 adriamycin(ADR) 농도를 $10^{-8}M$에서 $10^{-7}M$에 까지 적용시켜 내성세포주를 얻어 SUN-1/ADR로 나타내었으며 세포 성장은 SUN-1에서는 2일부터 6일까지 서서히 상승하였고 SNU-1/ADR은 $5{\times}10^3$celles/ml 농도 이상에서 상승을 보였다. 각 세포의 doubling 시간과 doubling 수를 비교하였으며 SNU-1은 doubling 시간이 평균 27.2 시간 doubling 수가 3.56번 이었으며, SNU-1/ADR은 52.2 시간 1.85번으로 내성세포가 더욱 성장이 왕성한 것을 관찰할 수 있다. MTT assay를 위하여 4일간의 성장으로 세포의 적절한 생존도를 관찰하였다. SNU-1과 내성세포주 SNU-1/ADR을 각각 항암제에 대한 약제 감수성 검사를 실시하였으며 약제농도 50%에서 생존도($IC_{50}$)를 비교하여 상관내성도(relative resistance : RR)을 측정 하였으며 vinblastine이 31.62이상으로 가장 높고, vincristine이 29.5, dactinomycin 21.37, epirubicin 17.78, daunorubicin 14.12였고, adriamycin 7.76이었으며 etoposide 4.46 이었다. 그 외의 약제 5-fluorouracil, cisplatin, cyclophosphamide, methotrexate, aclarubicin은 감수성이 낮았다. 위의 결과로 RR가 높은 약제들에 대해서는 multidrug resistance(복합내성)의 존재를 의미한다고 할 수 있으며 내성생성 SNU-1/ADR 세포주의 염색체의 검사에서 double minute chromosome(DMs)을 확인함으로서 내성 생성 세포를 확인 하였다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제13권4호
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• pp.391-404
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• 1991

Three anticncer agents which are different in time or dosage dependence as well as in phase specificity, namely mitomycin and adriamycin from natural products, and widely different cancer cell lines_Four epidermoid carcinomas originated from larynx, cervix, skin and gut were used toghether with one osteosarcoma as the target cell of single and combined administration of anticancer drugs. Semiautomated tetrazolium dye assay(MTT) appears to offer an attractive option for chemosensitivity of head and neck cancers since it is a simple, valid and inexpensive method of assessing chemosensitivity for large samples in a short time. The results obtained form this study were as follows. 1. Good correlations were obtained with the results of the MTT test and those of $^3H$ thymidine uptake assay. 2. $LD_{50}$ values of HIST and St.Ca. which showed relatively high doubling time on adriamycin were $30{\mu}g/ml$ and $15{\mu}g/ml$ while those of HeLa, Hep-2 and KHOS/NP were $2.1{\mu}g/ml$, $4.8{\mu}g/ml$, and $6.8{\mu}g/ml$ respectively. 3. The $LD_{50}$ value of 5-FU on five cancer cells were very high ranging from 15mg/ml to almost indefinite number, which means 5-FU is very resistant to epidermoid carcinomas or osteosarcoma examined in this study. 4. Mitomycin was relatively effective showing 80% cancer killing effect on HeLa, 70% on St. Ca. and 50% on Hep-2 at the high concentrations used. 5. Adriamycin was the most effective showing 90% cancer cell killing effect on KHOS/NP, 98% on HeLa, 80% both on Hep-2 and St. Ca. The least susceptible cancer cells toward adriamycin was HIST having only 55% cell killing effect at the high cincentration. 6. Combined therapy of adriamycin and 5-FU was more effective than single administration in all the cases examined. Most effective synergism was observed on St. Ca. at the low concentration, showing 21 times higher than each single administration.

• 한국식품영양과학회지
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• 제21권6호
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• pp.633-638
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• 1992

Adriamycin의 투여로 변화되는 생체내 지질과산화대사에 대하여 비타민 A및 E의 급여와 이들의 동시급여의 효과를 살펴보기 위해 이유한지 1주된 Sprague-Dawley 흰쥐를 6주간 사육하였다. 대조군을 제외한 모든 실험군에게 매주 일정시각에 ADR(2mg/kg/week)을 복강주사 한 후 비타민A와 E의 급여효과를 관찰하였으며 그 결과는 다음과 같다. 간 조직에서의 과산화지질 함량은 ADR투여로 현저한 증가로 보여주었고, 비타민 A 와 E급여가 이들의 생성을 저하시켰다. Catalase 활성도는 ADR의 투여로 증가된 반면 GSH-Px는 감소되는 경향이었다. 이에 비타민 A나 E의 급여로 ADR투여에 의한 효소 활성도의 변화를 완화시켰다. SOD의 활성은 ADR의 투여로 유의적인 변화는 나타나지 않았지만 비타민 A와 E동시 급여군에서 그 활성도가 현저히 유도외었다. 간 미토콘드리아의 지방산조정은 ADR투여로 큰 변화는 없었으나 비타민 E급여군이 비타민 A급여군 보다 방어효과가 더 좋았다. 또한 지질성분들의 변화는 ADR의 투여로 중성지질과 콜레스테롤 함량이 증가하였고 비타민 A의 급여에 의해 이들 함량이 유의적으로 감소되었다.

• Toxicological Research
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• 제16권2호
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• pp.101-107
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• 2000

Cannabidiol derivatives (1, 2 and 3), 5-fluorouracil (4, 5-FU) and adriamycin (5, AM) were tested for their growth inhibitory effects against human tumor cell lines using two different 3-{4,5-dimeth-ylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and sulforhodamine B protein (SRB) assay. The light microscopic study showed morphological changes of the treated cells. Disruptions in cell organelles were determined by colorimetric methods; MTT assay and STB assay. These results suggest that cannabidiol (1, CBD) retains the most growth-inhibitory activity against human tumor cell lines.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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• pp.37-37
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• 1993

1) 급성독성시험: 랫드와 마우스 공히 투여후 5~6일에 농도의존적의 강한 독성이 발현 되었으며 표적장기로는 소화기계, 임파계, 조혈기계 등으로 나타났다. 랫드에서의 반수 치사량은 암수 각각 771.9(505.6~1178.4)mg/kg과 479.8(302.7~760.4)mg/kg이었으며 마우스에서는 암수 각각 527.4(393.7~701.1)mg/kg과 463.0(308.8~694.2)mg/kg 이었다. 2) 유전독성: S. typhimurium을 이용한 복귀돌연변이시험, CHL세포를 이용한 염색체이상 시험, 마우스에서의 소핵시험결과 DA-125는 돌연변이 유발능을 갖는 것으로 나타났다. 3) 국소자극성: 혈관주위주사에 의한 피부자극성 시험결과 DA-125는 adriamycin의 3배 용량에서 궤양, 괴사등 유사한 병변이 유발되었으나, 병변회복은 adriamycin에 비해 빠른 것으로 나타났다. 또한 토끼에서의 안점막자극시험 결과에서 DA-125는 실제적으로 자극이 없는 것으로 나타났다.

• Applied Microscopy
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• 제19권2호
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• pp.99-118
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• 1989

The cardiotoxic effects of acute and chronic administration of adriamycin (ADR) were evaluated in A/J Swiss albino mice. In acute studies, male mice received intravenous ADR, 5mg or 15mg/kg per day for 3 or 1day and were sacrifice 12 hours later. Because the glutathione-glutathione peroxidase system is major pathway for free radical detoxication, glutathione levels and glutathione peroxidase activity was measured. In acute studies, ADR-treated mice exhibited significantly decreased levels(p<0.05) of total glutathione and unchanged levels of oxidized glutathione and percentage of oxidized glutathione. The earliest myocardial fine structural alterations included swelling and degeneration of mitochondria and dilatation of sarcoplasmic reticulum at all dosage of acute models. In chronic studies, mice received 5mg/kg ADR once a week for up to 16 weeks. Levels of total and reduced glutathione were decreased significantly(p<0.01) and oxidized glutathione and percentage of oxidized glutathione were increased significantly (p<0.05). Chronic myocardial lesions included perinuclear vacuolization, seperation of myofibrils and the fasciae adherens of intercalated disc and hypercontraction band within myocyte. Glutathione peroxidase activity reduced significantly (p<0.01) in any group of acute and chronic ADR-treated animals. Test for lipid peroxidation(malondialdehyde) was increased significantly(P<0.01). Thus, we conclude 1) ADR significantly lowers glutathione levels in heart tissue, and 2) cellular damage progress produced by alteration of this system in mouse models of ADR cardiotoxicity. These results suggest that the glutathione-glutathione peroxidase system may be involved in the modulation of ADR-induced cardiotoxicity.