• Biomolecules & Therapeutics
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• 제21권2호
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• pp.114-120
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• 2013

Most patients with mutant B-Raf melanomas respond to inhibitors of oncogenic B-Raf but resistance eventually emerges. To better understand the mechanisms that determine the long-term responses of mutant B-Raf melanoma cells to B-Raf inhibitor, we used chronic selection to establish B-Raf (V600E) melanoma clones with acquired resistance to the new oncogenic B-Raf inhibitor UI-152. Whereas the parental A375P cells were highly sensitive to UI-152 ($IC_{50}$ < $0.5{\mu}M$), the resistant sub-line (A375P/Mdr) displayed strong resistance to UI-152 ($IC_{50}$ < $20{\mu}M$). Immunofluorescence analysis indicated the absence of an increase in the levels of P-glycoprotein multidrug resistance (MDR) transporter in A375P/Mdr cells, suggesting that resistance was not attributable to P-glycoprotein overexpression. In UI-152-sensitive A375P cells, the anti-proliferative activity of UI-152 appeared to be due to cell-cycle arrest at $G_0/G_1$ with the induction of apoptosis. However, we found that A375P/Mdr cells were resistant to the apoptosis induced by UI-152. Interestingly, UI-152 preferentially induced autophagy in A375P/Mdr cells but not in A375P cells, as determined by GFP-LC3 puncta/cell counts. Further, autophagy inhibition with 3-methyladenine (3-MA) partially augmented growth inhibition of A375P/Mdr cells by UI-152, which implies that a high level of autophagy may protect UI-152-treated cells from undergoing growth inhibition. Together, our data implicate high rates of autophagy as a key mechanism of acquired resistance to the oncogenic B-Raf inhibitor, in support of clinical studies in which combination therapy with autophagy targeted drugs is being designed to overcome resistance.

• 한국식품영양과학회지
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• 제24권5호
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• pp.790-795
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• 1995

응집제를 생산하는 미생물은 토양시료로 부터 분리하여 그 중 응집활성이 높은 1 균주를 선택하여 분류학적 위치를 조사한 결과, Arcuadendrop sp.으도 동정되었으며 본 균주를 Arcuadendron sp. TS-49로 명명하였다. 응집제 생산 최적배지는 3% glucose, 0.2% yeast extract, 0.1% $NH_4Cl$, 0.05% $MnSO_4$, 0.01% $MgSO_4$ (pH 7.0)의 경우가 가장 우수하였으며, 배양 온도 및 배양 pH는 $30^{\circ}C$, pH 7.0일 때가 최적이었다. 최적 배양조건하에서 4~5일간 배양시 응집제 생산량이 최대에 도달하였으며 배양 시간의 경과와 더불어 응집활성은 급격히 감소하는 현상을 보여 생분해성이 우수함을 나타내었따. 이때의 응집제 생산량은 screening 배지에 비해 거의 10배 정도로 향상되었으며, 각종 microorganism과 suspended solid에 대한 응집작용을 검토한 결과, 정도의 차이는 있으나 모든 공시물질에 응집활성을 나타내었다.응집제의 조성을 검토하기 위해 각종 정성 test를 행한 결과, 당과 단백질이 검출되어 일종의 glycoprotein 임이 확인되었다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3447-3450
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• 2015

Objective: To explore the sensitivity of gastric cancer cells to chemotherapy drugs in elderly patients and its correlation with cyclooxygenase-2 (COX-2) expression in cancer tissue. Materials and Methods: Forty-three elderly patients with gastric cancer (observation group) and 31 young patients with gastrointestinal tumors (control group) who were all diagnosed by pathology and underwent surgery in the 89th Hospital of Chinese People's Liberation Army were selected. Drug sensitivity testing of tumor cells in primary culture was carried out in both groups using a methyl thiazolyl tetrazolium (MTT) method, and the expression of COX-2 and the factors related to multi-drug resistance (MDR) in cancer tissue were assessed by immunohistochemistry. Results: The inhibition rates (IR) of vincristine (VCR), 5-fluorouracil (5-FU), oxaliplatin (L-OHP), mitomycin (MMC) and epirubicin (eADM) on tumor cells in the observation group were dramatically lower than in the control group, with statistical significance (P<0.05 or P<0.01). The positive rates of COX-2, glutathione s-transferase-${\pi}$ (GST-${\pi}$) and P glycoprotein (P-gp) expression in cancer tissue in the observation group were all higher than in control group (P<0.05), while that of DNA topoisomerase $II{\alpha}$ ($TopoII{\alpha}$) expression lower than in the control group (P<0.01). In the observation group, COX-2 expression in cancer tissue had a significantly-positive correlation with GST-${\pi}$ and P-gp (r=0.855, P=0.000; r=0.240, P=0.026), but a negative correlation with $TopoII{\alpha}$ (r=-0.328, P=0.002). In the control group, COX-2 expression in cancer tissue was only correlated with P-gp positively (r=0.320, P=0.011). Bivariate correlation analysis displayed that COX-2 expression in cancer tissue in the observation group had a significantly-negative correlation with the IRs of 5-FU, L-OHP, paclitaxel (PTX) and eADM in tumor cells (r=-0.723, P=0.000; r=-0.570, P=0.000; r=-0.919, P=0.000; r=-0.781, P=0.000), but with hydroxycamptothecine (HCPT), VCR and 5-FU in the control group (r=-0.915, P=0.000; r=-0.890, P=0.000; r=-0.949, P=0.000). Conclusions: Gastric cancer cells in elderly patients feature stronger MDR, which may be related to high COX-2 expression.

• Journal of Pharmaceutical Investigation
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• 제34권4호
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• pp.283-288
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• 2004

The pharmacokinetics of nifedipine was studied after oral coadministration of nifedipine (5 mg/kg) with quercetin (1.5, 7.5, 15 and 30 mg/kg, respectively) and 0.5 h or 3days pretreatment with quercetin (1.5 and 7.5mg/kg) in rabbits. Pretreatment of quercetin significantly (p<0.05, at 0.5 h; p<0.01, at 3 days) increased the plasma concentration of nifedipine, but not significant in coadministraiton. The area under the plasma concentration-time curve (AUC) and the peak concentration $(C_{max})$ of nifedipine pretreated with quercetin were increased significantly (p<0.05, at 0.5 h; p<0.01, at 3 days) compared to the control. By coadministration of quercetin, only 7.5 mg/kg of quercetin increased plasma AUC and $C_{max}$ of nifedipine significantly (p<0.05) compared to the control. Plasma AUC of intravenous nifedipine (1 mg/kg) is $4235\;{\pm}\;1192\;ng/ml{\cdot}hr$. Pretreatment of quercetin significantly (p<0.05, at 0.5 h; p<0.01, at 3 days) increased the absolute bioavailability (AB%) of nifedipine to 23.9-29.2% compared to the control (17.8%). Coadministration of quercetin showed no significant effect on the AB% of nifedipine except for 7.5 mg/kg. It is suggested that quercetin alters disposition of nifedipine by inhibition of P-glycoprotein efflux pump and its first-pass metabolism. The dosage of nifedipine should be adjusted when it is administered chronically with quercetin in a clinical situation.

• 한국수산과학회지
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• 제47권6호
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• pp.765-769
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• 2014

We examined the protective effects of Pyropia yezoensis glycoprotein (PYGP) against ethanol-induced gastric damage. The experimental animals were divided into four groups. They were treated with distilled water (control), ethanol alone (EtOH), ethanol + PYGP 150 mg/kg BW (EtOH+150), or ethanol + PYGP 300 mg/kg BW (EtOH+300). The groups were treated for 4 weeks. We measured mitogen-activated protein kinase (MAPK), the apoptotic signaling pathway, and PARP activity in gastric tissues obtained from the rats. Ethanol consumption increased apoptotic signal activity and ERK, JNK, and p38 phosphorylation. PYGP reduced the apoptotic signaling pathway activity and ERK, JNK, and p38 phosphorylation. Furthermore, PYGP regulated Bcl-2 family expression. In light of these findings, PYGP appears to prevent ethanol-induced gastric injury and oxidative stress.

• 생명과학회지
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• 제24권12호
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• pp.1316-1324
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• 2014

신령버섯균사체(Agaricus blazei mycelia: ABM)를 대두박이 함유된 액체배지에 배양하고, 이것을 자가분해($53^{\circ}C$, pH 5.5, 120 rpm, 3 hr)하여 항암성이 강한 isoflavone-conjugated glycoprotein (Gluvone 이라 명명)을 분리하였다. Gluvone은 지금까지 알려진 당단백질과는 달리 분자량이 작고(9,400 Da), isoflavone이 결합되어 있다는 점이 다르다, Gluvone은 60% 탄수화물(glucose, fructose, ribose), 31% 단백질 및 2% isoflavone (daidzein, genistein)으로 구성되어 있었다. 이 Gluvone은 S-180 복수암세포, MCF-7 인체유선암세포에 대한 독성이 강하였고, S-180 세포로 유발한 mouse 복수암을 강하게 억제하였다.

• 한국응용과학기술학회지
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• 제29권2호
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• pp.257-267
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• 2012

본 연구에서 당근에서 제조한 CG의 기능성 화장품 소재로서의 응용성을 SCP와 비교 검토하기 위하여 CG와 SCP를 적용한 각각의 기능성 크림을 제조하였다. CG와 SCP를 적용한 각각의 기능성 크림에서의 변색, 변취 및 크리밍 현상이나 응집 등의 관능검사와 pH, 점도 등의 물성 변화는 $5^{\circ}C$, $25^{\circ}C$에서 매우 안정하다. 피부에서의 수분손실량 및 수분 함유량의 변화를 측정한 결과에서도 CG의 보습작용이 우수한 것으로 나타났다. 이러한 결과를 토대로 CG를 함유한 크림은 SCP를 함유한 크림과 마찬가지로 피부에 보습 효과가 우수하여 주름개선에도 큰 영향을 줄 것으로 예상된다.

• 약학회지
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• 제50권4호
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• pp.272-277
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• 2006

This study was undertaken to determine whether the 9 herbal complex induces apoptosis in human breast cancer MCF-7 cells and adriamycin-resistant MCF7/adR cells. Ethanol extracts of Bojungbangamtang (BBTE) and acidic polysaccharide of Red Ginseng (GIN) induced cell death in both MCF-7 and MCF7/adR cells. Ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng also induced $G_2/M$ cell cycle arrest and increased TUNEL positive cells in MCF7/adR cells. In addition, flow cytometric analysis revealed the decreased expression of P-glycoprotein (P-gp) in ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng treated MCF7/adR cells. Similarly, decreased protein levels of P-glycoprotein and multidrug resistance associated proteins-1 were also determined by immunocytometry in ethanol extracts of Bojungbangamtang treated MCF7/adR cells. Taken together these data indicate that ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng inhibit the function of ABC transporters such as multi drug resistance associated proteins (MRPs) and P-glycoprotein as well as induce apoptosis in MCF7/adR cells. Thus, these data suggest that ethanol extracts of Bojungbangamtang and polysaccharide of Red Ginseng can be candidates for the treatment of multidrug-resistant MCF7/adR cells.

• Biomolecules & Therapeutics
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• 제19권2호
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• pp.174-180
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• 2011

Experiments were carried out to determine the role of Raf-1 kinase in the development of drug resistance to paclitaxel in v-H-ras transformed NIH 3T3 fibroblasts (Ras-NIH 3T3). We established a multidrug-resistant cell line (Ras-NIH 3T3/Mdr) from Ras-NIH 3T3 cells by stepwise increases in paclitaxel. Drug sensitivity assays indicated that the $IC_{50}$ value for drug-resistant Ras-NIH 3T3/Mdr cells was more than 1 ${\mu}M$ paclitaxel, 10- or more-fold higher than for the parental Ras-NIH 3T3 cells. Western blot and RT-PCR analysis showed that the drug efflux pump a P-glycoprotein were highly expressed in Ras-NIH 3T3/Mdr cells, while not being detectable in Ras-NIH 3T3 cells. Additionally, verapamil, which appears to inhibit drug efflux by acting as a substrate for P-glycoprotein, completely reversed resistance to paclitaxel in Ras-NIH 3T3/Mdr cell line, indicating that resistance to paclitaxel is associated with overexpression of the multidrug resistance gene. Interestingly, Ras-NIH 3T3/Mdr cells have higher basal Raf-1 activity compared to Ras-NIH 3T3 cells. Unexpectedly, however, the colocalization of Raf-1 and its negative regulator Spry2 was less observed in cytoplasm of Ras-NIH 3T3/Mdr cells due to translocation of Spry2 around the nucleus in the perinuclear zone, implying that Raf-1 may be released from negative feedback inhibition by interacting with Spry2. We also showed that shRNA-mediated knockdown of Raf-1 caused a moderate increase in cell susceptibility to paclitaxel. Thus, the results presented here suggest that a Raf-1-dependent pathway plays an important role in the development of acquired drug-resistance.

• Clinical and Experimental Reproductive Medicine
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• 제35권4호
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• pp.267-274
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• 2008

목 적: 한국 여성에서 alpha2-Heremans Schmidt glycoprotein (AHSG) 유전자 다형성과 중증 자궁내막증의 연관성을 알아보고자 하였다. 연구방법: 자궁내막증이 없는 여성 224명과 중증 자궁내막증이 있는 여성 130명을 대상으로 하였다. 모든 여성은 복강경이나 개복수술을 시행하여 수술 소견 및 조직학적 진단으로 중증 자궁내막증의 존재 여부를 진단하였다. 환자군과 대조군의 혈액을 채취하였고 AHSG 유전자 다형성을 중합효소연쇄반응 (PCR) 및 제한효소 절편길이 다형성(restriction fragment length polymorphism; RFLP) 분석으로 조사하였다. 결 과: 자궁내막증 환자군에서 AHSG 1*1 유전자형의 빈도는 56.2% (73/130), AHSG 1*2 유전자형은 37.7% (49/130), AHSG 2*2 유전자형은 6.2% (8/130)로 정상 대조군의 55.8% (125/224), 39.3% (88/224), 4.9% (11/224)의 빈도와 차이가 없었다 (p=.864). 또한 AHSG 2 일배체형의 빈도 역시 환자군에서 25.0% (65/260), 대조군 24.6% (110/448)로 두 군간에 유의한 차이가 없었다 (p=.894). 결 론: 한국 여성에서 AHSG 유전자 다형성과 자궁내막증은 연관이 없었다.