• 한국임상수의학회지
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• 제18권1호
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• pp.14-17
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• 2001

Recombinant interleukin-2 (IL-2) has demonstrated as an antineoplastic agent in mice and human, but the relatively low response rates observed in clinical trials. Therefore, the present study was undertaken in order to evaluate therapeutic activities of IL-2 for the establishment of therapeutic applications. At the onset of the experiment, normal C3H/HeN mice were injected with $3{\times}10^6$ RD-995 tumor cells, murine ultraviolet radiation-induced fibrosarcoma, subcutaneously. Beginning on day 25, experimental groups were treated with a 5-day course of IL-2 (subcutaneous injection of 30,000 IU every 12 hours for 5 days). The result of this experiment revealed that RD-995 tumor grew progressively in control mice. Subcutaneous IL-2 therapy decreased tumor growth until day 23, then the tumor grew progressively. No significant difference in the survival of IL-2 therapy decreased tumor growth until day 23, then the tumor grew progressively. No significant difference in the survival of IL-2 therapy decreased tumor growth until day 23, then the tumor grew progressively. No significant difference in the survival of IL-2 treated mice were observed compared with the control mice.

• Biomolecules & Therapeutics
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• 제3권1호
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• pp.38-46
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• 1995

DA-125, a new anthracycline antitumor antibiotic, was administered at dose levels of 0, 0.04, 0.2 and 1.0 mg/kg/day intravenously to pregnant and subsequently delivered Sprague-Dawley rats from day 17 of gestation to day 21 of lactation. Effects of test agent on general toxicity of dams and growth, behaviour and mating performance of F1 offspring were examined. At 1 mg/kg, one out of the twentytwo dams showed difficult delivery, characterized by a stillbirth. Reduction in body weight, loss in food intake, and decrease in spleen weight were also observed in dams. In addition, the lower rates of successful performances in memory test (28.6%) and necrosis of tail end (9.5%) were seen in F1 offspring. At 0.04 and 0.2 mg/kg, no toxic effect on dams and F1 offspring was observed. There were no malformed Fl and F2 fetuses in all groups. The results indicate that the no effect dose levels(NOELs) of DA-125 are 0.2 mg/kg/day for dams and Fl offspring, and over 1 mg/kg/day for F2 fetuses.

• 한국한의학연구원논문집
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• 제8권2호통권9호
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• pp.109-119
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• 2002

The objective on this study was to investigate effect of KH, which was composed of 9 kinds of oriental herbs tonifing the blood, against toxicity of 5-flurouracil(FU) through animal study. Reduction of WBC and platelet after treating S-FU was significantly recovered by KH. KH also rehabilitated immune gene expression of interleukin-2(IL2) and $Interferon-{\gamma}\;(IFN-{\gamma})$ by RT-PCR. In addition, in situ hybridization of spleen showed that KH treatment increased mRNA expression of IL2. In addition to the immune action, antitumor activity on 5-FU was not affected by KH treatment. In conclusion, our study demonstrated that KH alleviated damage of hematopoiesis system induced by f-FU without toss of antitumor activity.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6075-6080
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• 2014

Lung cancer is the leading cause of cancer-related death worldwide. Here we investigated the antitumor effect and mechanism of Zhejiang (Huzhou and Jiande) saffron against lung cancer cell lines, A549 and H446. Using high performance liquid chromatography (HPLC), the contents of crocin I and II were determined. In vitro, MTT assay and annexin-V FITC/PI staining showed cell proliferation activity and apoptosis to be changed in a dose- and time-dependent manner. The inhibition effect of Jiande saffron was the strongest. In vivo, when mice were orally administered saffron extracts at dose of 100mg/kg/d for 28 days, xenograft tumor size was reduced, and ELISA and Western blotting analysis of caspase-3, -8 and -9 exhibited stronger expression and activity than in the control. In summary, saffron from Zhejiang has significant antitumor effects in vitro and in vivo through caspase-8-caspase-9-caspase-3 mediated cell apoptosis. It thus appears to have more potential as a therapeutic agent.

• KSBB Journal
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• 제6권1호
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• pp.45-54
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• 1991

The aims of this study were investigated the antitumor effects and immunological activities of lipopolysaccharides (LPS) extracted from Proteus vulgaris RH-90 toward sarcoma-180 cells. LPS extracted from Proteus vulgris RH-90 was irradiated with gamma ray for detoxification. The tumor incidence of sarcoma-180 occurs all group which injected with gamma ray irradiated LPS and tumor of sarcoma-180 was necrotized with breeding in the injected group of l0$\mu\textrm{g}$ LPS. The inhibition ratio of tumor growth showed at the highest level of 60.88% when 5$\mu\textrm{g}$ gamma ray irradiated LPS was injected into mice. The prolongation ratio of life showed 20.72% when injected into mice with gamma ray irradiated LPS of 5$\mu\textrm{g}$. In the effect of immunological activity, the number of circurating leucocyte and peritoneal exudate cells were increased significantly in the treatment group than that control group, and dose-dependent response indicated by the increase of weights of immunorgans which revealed the improvement of immunity. The effect of macrophage on phagocytes, there were not found the differences between phagocytic and corrected phagocytic index.

• 동의생리병리학회지
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• 제16권3호
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• pp.542-546
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• 2002

The purpose of this study was to investigate the effect of 2-thioDMNQ-S160, shikonin analogue isolated from Uthospermum Erythrorhizon, on the antitumor activity. In the present study, 2-thioDMNQ-S160 exhibited a significant cytotoxicity against L1210, A549, U937, and 816-BL6 cell lines with IC/sub 50/s of 2.4ug/ml, 2,0ugjml. 4ug/ml and 20 ug/ml, respectively. 2-ThioDMNQ-S160 strongly inhibited adhesion of B16-BL6 cells to gelatin and matrigel coated matrices. Also, 2-ThioDMNQ-S160 exhibited anti-invasive effect of B16-BL6 cells. The T/C% was 123 % in 2-ThioDMNQ-S160 treated group in S-180 bearing ICA mice. These results suggested that 2-thioDMNQ-S160 might be a potent candidate of cancer drug.

• 한국임상수의학회지
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• 제28권6호
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• pp.549-554
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• 2011

FK506은 말기 간암환자의 간이식 후 널리 사용되는 면역억제제이다. Dexamethasone은 세포독성 암 치료에서 오심 방지, 정상세포의 보호와 기타 이유 등의로 빈번하게 병용처치된다. 본 연구의 목적은 간암세포주(Hep3B)에서 FK506의 항암효과와 FK506에 의한 항암효과에 대한 dexamethasone의 억제효과를 알아보기 위함이다. 세포의 손상은 세포 생존성 평가와 LDH 및 세포내 ROS 양의 측정으로 평가 하였다. 세포내 칼슘 농도([$Ca^{2+}$]i)와 JNK, Bax 단백질의 발현 정도도 평가하였다. FK506의 처치는 Hep3B의 세포사를 유도하였으며 세포생존성의 감소와 LDH, ROS 및 [$Ca^{2+}$]i 를 증가시켰다. FK506은 Bax와 JNK 의 활성을 증가시켰으며 Bcl-2의 활성을 억제하였다. Dexamethasone 처치 그 자체는 세포생존성, LDH와 ROS에 영향을 주지 않았다. 그러나 dexamethasone과 FK506의 병용처치는 FK506에 의한 LDH 방출, ROS 생성 및 JNK의 활성을 감소시켰다. 이 결과는 간암세포주에서 FK506은 항암효과를 가지지만 dexamethasone의 병용처치는 FK506에 의한 항암효과를 길항한다.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.718-723
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• 2002

CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin) is a recently-developed synthetic camptothecin analogue and currently under clinical development by Chong Kun Dang Pharm (Seoul, Korea). CKD-602 showed potent topoisomerase inhibitory activity in vitro and broad antitumor activity against various human tumor cells in vitro and in vivo in animal models. This study describes the pharmacodynamics of the immediate and delayed cytotoxicity induced by CKD-602 in a human colorectal adenocarcinoma cell line, HT-29, and its intracellular drug accumulation by HPLC. The present study was designed to address whether the higher activity of CKD-602 with prolonged exposure is due to delayed exhibition of cytotoxicity and/or an accumulation of anti proliferative effect on continuous drug exposure. The drug uptake study was performed to determine whether the delayed cytotoxicity is due to a slow drug accumulation in cells. CKD-602 produced a cytotoxicity that was exhibited immediately after treatment (immediate effect) and after treatment had been terminated (delayed effect). Both the immediate and delayed effects of CKD-602 showed a time dependent decrease in 4IC_{50}$ values. Drug uptake was biphasic and the second equilibrium level was obtained as early as at 24hr, indicating that the cumulative and delayed antitumor effects of CKD-602 were not due to slow drug uptake. On the other hand, CKD-602 treatment was sufficient to induce delayed cytotoxicity after 4hr, however, longer treatment (＞24hr) enhanced its cytotoxicity due to the intracellular accumulation of the drug, which requires 24hr to reach maximum equilibrium concentration. In addition, $C^n$$\times$T=h analysis (n=0.481) indicated that increased exposure times may contribute more to the overall antitumor activity of CKD-602 than drug concentration. Additional studies to determine the details of the intracellular uptake kinetics (e.g., concentration dependency and retention studies) are needed in order to identify the optimal treatment schedules for the successful clinical development of CKD-602.

• 한국식품영양과학회지
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• 제28권4호
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• pp.917-923
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• 1999

개불 당단백질의 sarcom 180 cell 고형암 성장 저지능은 4mg/kg에서 43.63%로 나타났으나, 20mg/kg이상의 농도에서는 고형암 성장 저지능을 보이지 않았다. Sarcom 180 cell에 대한 수명 연장 실험에서도 2mg/kg와 4mg/kg의 저농도에서는 상당한 수명연장 효과를 보였으나, 2Omg/kg 이상의 고농도 투여군에서는 수명연장 효과를 나타내지 않았다. 개불 당단백질의 sarcoma 180 cell에 대한 직접적인 세포 독성 효과는 농도의 증가에 따라 약간의 종양세포 살해효과를 보였으나, 그 효과는 미약하였다. 개불 당단백질의 면역능 증진효과는 체중에 대한 간과 비장의 중량비 증가, 총 복강세포수의 증가 그리고, 당단백질을 고농도 투여시 30.78%~46.30%정도의 백혈구 수 증가 등으로 확인되었다. 이러한 결과로서 개불에서 추출한 당단백질의 항암효과는 면역활성의 증진과 면역자극의 효과라고 볼 수 있었으나, 전반적인 면역활성의 증가에도 불구하고, sarcoma 180 cell에 대한 고형암 성장 저지실험과 수명연장실험에서 고농도로 투여시에는 오히려 활성이 나타나지 않았다. 따라서 개불 당단백질의 최적투여 농도와 고농도 투여시의 부작용에 관한 더 많은 연구가 필요하였다. 이상의 결과에서 개불에서 추출한 당단백질의 면역자극에 의한 항종양 활성을 확인 되므로, 일반적으로 사용되어지는 항암 화학요법제와 더 불어 병행될 수 있는 면역증진제로서의 개발 가능성이 있다고 보여진다.

• 동의생리병리학회지
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• 제17권3호
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• pp.819-825
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• 2003

pharbitis nil and Taraxacum mongolicum are representative herbs that have been used for cancer treatment in Korean traditional medicine. To understand the molecular basis of the antitumor function, we analyzed the effect of these herbs on proliferation and apoptosis of tumor cells using a gastric cancer cell line AGS. Cell counting assay showed that pharbitis nil strongly inhibit cell proliferation Of AGS whereas Taraxacum mongolicum exhibit no detectable effect on cellular growth. [³H]thymidine uptake analysis also demonstrated that DNA replication of AGS is suppressed in a dose-dependent manner by treatment with pharbitis nil. Additionally, tryphan blue exclusion assay showed that Pharbitis nil induce apoptotic cell death of AGS in a dose-dependent. To explore whether anti antiproliferative and/or proapototic property of Pharbitis nil is associated with their effect on gene expression, we performed RT-PCR analysis of cell cycle- and apoptosis-related genes. Interestingly, mRNA expression levels of c-Jun, c-Fos, c-Myc, and Cyclin D1 were markedly reduced by Pharbitis nil. Taraxacum mongolicum also showed inhibitory action on expression of these growth-promoting protooncogene but there effects are less significant, as compared to Pharbitis nil. Furthermore, it was also found that Pharbitis nil activates expression of the p53 tumor suppressor and its downstream effector p21Waf1, which induce G1 cell cycle arrest and apoptosis. Collectively, our data demonstrate that Pharbitis nil induce growth inhibition and apoptosis of human gastric cancer cells and these effects are accompanied with down-and up-regulation of growth-regulating protooncogenes and tumor suppressor genes, respectively. This observation thus suggests that the anticancer effect of Pharbitis nil might be associated with its regulatory capability of tumor-related gene expression.