• Development and Reproduction
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• v.25 no.2
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• pp.93-104
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• 2021

Cutaneous melanoma is a fatal disease for patients with distant metastasis. Metformin is the most widely used anti-diabetic drug, and proved to suppress cell proliferation and metastasis in diverse cancers including melanoma. We previously reported that MEK inhibitor trametinib increases the expression of epithelial-mesenchymal transition (EMT) regulators and melanoma cell motility, which are suppressed by addition of metformin in A375 melanoma cells. To confirm our findings further, we first evaluated the effect of metformin in combination with another MEK inhibitor binimetinib on cell viability in G361 melanoma cells. We then investigated whether binimetinib affects the expression of EMT regulators and cell motility. We finally monitored the effect of metformin on binimetinib-induced cell migration. Cell viability assay showed that combination index (CI) value at ED₅₀ is 0.80, suggesting synergy for the combination of metformin with binimetinib. Our results also revealed that binimetinib increased the expression of EMT regulators such as integrin αV, fibronectin and slug, which correlate well with the enhanced cell migration in wound healing assay. Metformin, on the contrary, suppressed the expression of sparc, integrin αV, fibronectin and N-cadherin with the reduced cell motility. The combination treatment showed that metformin counteracts the binimetinib-induced increase of cell motility. Overall, these results suggest that metformin with binimetinib might be useful as a potential therapeutic adjuvant against cell survival and metastatic activity in melanoma patients.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.527-538
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• 2019

Background: Ginsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor (ER) via mitogen-activated protein kinase-mediated pathway. Our study aimed to delineate the mechanisms by which Rg1 activates the rapid ER signaling pathways. Methods: ER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidney HEK293 cells were treated with Rg1 ($10^{-12}M$, $10^{-8}M$), $17{\beta}$-estradiol ($10^{-8}M$), or vehicle. Immunoprecipitation was conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or their inhibitors were applied. Results: Rg1 rapidly induced $ER{\alpha}$ translocation to plasma membrane via caveolin-1 and the formation of signaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator of nongenomic activity of ER (MNAR), $ER{\alpha}$, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase (MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interfering RNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in these cells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor (EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). The increase in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could be abolished by G15. Conclusion: Ginsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.

• Journal of the Korean Institute of Electrical and Electronic Material Engineers
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• v.27 no.11
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• pp.736-739
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• 2014

In this paper, we propose a enhanced anti-corrosion property of the ground system by coating the CNT/PVDF composite film on it. Polymer material used for preventing the corrosion of ground system is polyvinylidene fluoride (PVDF), and conducting filler for obtaining conductivity of the composite film is multi-walled carbon nanotubes (MWCNTs). The MWCNTs were dispersed in the organic solvent of methyl ethyl ketone 2-butanone (MEK) with different concentration ratios, and the PVDF was solved in the MEK solvent with constant concentration ratio of 1 wt%. The CNT/PVDF composite solution was perpared by mixing and re-dispersing the CNT solution and the PVDF solution. Finally, the CNT/PVDF composite films were fabricated by the spray coating method using the above composite solution. Electrical conductivity, surface states, and anti-corrosion property of the CNT/PVDF composite films coated on the Cu substrate were evaluated. We found that the CNT/PVDF composite film showed relatively low resistance, hydrophobic surface state, and chemical stability. Consequently, we could improve the anti-corrosion property and maintain the electrical conductivity of the ground system by coating the CNT/PVDF composite film on it.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8539-8548
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• 2014

Mitogen-activated protein kinase (MAPK) is an important signaling pathway in living beings in response to extracellular stimuli. There are 5 main subgroups manipulating by a set of sequential actions: ERK(ERK1/ERK2), c-Jun N(JNK/SAPK), p38 MAPK($p38{\alpha}$, $p38{\beta}$, $p38{\gamma}$ and $p38{\delta}$), and ERK3/ERK4/ERK5. When stimulated, factors of upstream or downstream change, and by interacting with each other, these groups have long been recognized to be related to multiple biologic processes such as cell proliferation, differentiation, death, migration, invasion and inflammation. However, once abnormally activated, cancer may occur. Several components of the MAPK network have already been proposed as targets in cancer therapy, such as p38, JNK, ERK, MEK, RAF, RAS, and DUSP1. Among them, alteration of the RAS-RAF-MEK-ERK-MAPK(RAS-MAPK) pathway has frequently been reported in human cancer as a result of abnormal activation of receptor tyrosine kinases or gain-of-function mutations in genes. The reported roles of MAPK signaling in apoptotic cell death are controversial, so that further in-depth investigations are needed to address these controversies. Based on an extensive analysis of published data, the goal of this review is to provide an overview on recent studies about the mechanism of MAP kinases, and how it generates certain tumors, as well as related treatments.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1077-1082
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• 2015

Recent studies have suggested that the RAS protein activator like-1 (RASAL1) functions as a tumor suppressor in vitro and may play an important role in the development of gastric cancer. However, whether or not RASAL1 suppresses tumor growth in vivo remains to be determined. In the present study, we investigated the role of RASAL1 in gastric carcinogenesis using an in vivo xenograft model. A lentiviral RASAL1 expression vector was constructed and utilized to transfect the human poorly differentiated gastric adenocarcinoma cell line, BGC-823. RASAL1 expression levels were verified by quantitative real-time RT-PCR and Western blotting analysis. Then, we established the nude mice xenograft model using BGC-823 cells either over-expressing RASAL1 or normal. After three weeks, the results showed that the over-expression of RASAL1 led to a significant reduction in both tumor volume and weight compared with the other two control groups. Furthermore, in xenograft tissues the increased expression of RASAL1 in BGC-823 cells caused decreased expression of p-ERK1/2, a downstream moleculein the RAS/RAF/MEK/ERK signal pathway. These findings demonstrated that the over-expression of RASAL1 could inhibit the growth of gastric cancer by inactivation of the RAS/RAF/MEK/ERK pathway in vivo. This study indicates that RASAL1 may attenuate gastric carcinogenesis.

• Reproductive and Developmental Biology
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• v.35 no.4
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• pp.449-455
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• 2011

Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by etopic expression of transcription factors. iPS cells are indistinguishable from ES cells in terms of morphology and stem cell marker expression. Moreover, mouse iPS cells give rise to chimeric mice that are competent for germline transmission. However, mice derived from iPS cells often develop tumors. Furthermore, the low efficiency of iPS cell generation is a big disadvantage for mechanistic studies. Nonviral plasmid.based vectors are free of many of the drawbacks that constrain viral vectors. The histone deacetylase inhibitor valproic acid (VPA) has been shown to improve the efficiency of mouse and human iPS cell generation, and vitamin C (Vc) accelerates gene expression changes and establishment of the fully reprogrammed state. The MEK inhibitor PD0325901 (Stemgent) has been shown to increase the efficiency of the reprogramming of human primary fibroblasts into iPS cells. In this report, we described the generation of mouse iPS cells devoid of exogenous DNA by the simple transient transfection of a nonviral vector carrying 2A-peptide-linked reprogramming factors. We used VPA, Vc, and the MEK inhibitor PD0325901 to increase the reprogramming efficiency. The reprogrammed somatic cells expressed pluripotency markers and formed EBs.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.15 no.3
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• pp.261-269
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• 2005

To investigate the field applicability of a diffusive sampler (3M OVM #3500, passive sampling method) authors conducted a simultaneous measurement of personal organic solvents exposure in the air of the workplaces by charcoal tube with low volume sampler (active sampling method) and diffusive sampler. Samples were collected and analyzed by NIOSH method ($NMAM^{(R)}$) from thirty-eight workers in 12 factories who work in 6 different processes. Geometric mean (GM) and geometric standard deviation (GSD) were used to describe the result. To compare the results of the two methods, paired t-test was used. According to the manual of the exposure assessment of the mixed organic solvents (Ministry of Labor, Korea), Em was calculated. Simple linear regression was used to evaluate the relationship between the two methods. Results were as follows; 1. Eight different solvents (ethyl acetate, n-hexane, toluene, xylene, acetone, isopropyl alcohol, methyl ethyl ketone (MEK), and methyl isobutyl ketone) were detected simultaneously in the two methods and the concentrations of the personal exposure were lower than 0.5 TLV level. The concentration of the charcoal tube method was higher than that of a diffusive sampler in n-hexane and MEK (p<0.05). 2. Em of the charcoal tube method was higher than that of diffusive sampler method but not significantly different and was lower than the OEL (Occupational Exposure Limit) in all 6 processes. 3. There was a significant correlation between the two methods in low concentrations of the 8 organic solvents (p<0.05). In conclusion, there was no difference in charcoal tube method and diffusive sampler method in low concentrations of some organic solvents, diffusive sampler can be applied to assess the personal monitoring in low level exposure.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.13 no.8
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• pp.3764-3773
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• 2012

In this study, modeling and optimization works were completed for the separation of 99.9 mol% of methyl ethyl ketone from water through a pressure-swing distillation process since the azeotropic composition varies very sensitively with the change of system pressure. PRO/II with PROVISION release 9.1 was used for the computer simulation and Wilson activity coefficient model was chosen as a modeling equation. A pressure-swing distillation process can be classified into a low-high pressure columns configuration and a high-low pressure columns configuration. In this work, each configurations were optimized for the minimization of steam consumptions, respectively and were compared.

• Biomedical Science Letters
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• v.17 no.4
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• pp.291-295
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• 2011

PD98059 is the specific inhibitor of extracellular signaling-regulated kinase (ERK) kinase (MEK). ERK is involved in a mitogen-activated protein kinase (MAPK) cascade controlling cell growth and differentiation. Although the inhibition of ERK is known to induce cell death in various cell lines, this effect is still controversial and the role of PD98059 on the death of HeLa $S_3$ cells, a subclone of the cervical cancer cell line, is not well understood. The apoptosis of HeLa $S_3$ cells increased after the treatment of 50 ${\mu}M$ PD98059. The induction of apoptosis by PD98059 was occurred in a time- and a dose-dependent manners. The expression of Bcl-2 was reduced in accordance with decrease of ERK2 expression. Taken together, these results indicate that PD98059 has a cytotoxicity in HeLa $S_3$ cells and it may be used as a potential target for the treatment of cervical cancer.

• Proceedings of the Korean Nuclear Society Conference
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• 1997.10a
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• pp.778-783
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• 1997

원자력 발전소에서의 중대사고시, 고온의 노심 용융물이 원자로 공동으로 떨어지면 노심용융물과 콘크리트간의 반응(MCCI)에 의한 여러가지 현상으로 인해 격납용기의 건전성을 위협할 수 있다. 본 연구에서는 국내 영광원전 3, 4호기에 사용된 공동구조물 콘크리트와 고온용융물간의 반응특성을 실험적으로 살펴보았다. 실험은 유도가열로를 이용한 1차원 장기침식을 모사하기 위한 MEK-S1 실험이다. 실험에서는 유도로의 전원부족으로 용융풀을 형성하지 못하여 장기침식에는 실패하였다. 하지만 약 150$0^{\circ}C$의 고온 SUS 304에 의한 콘크리트의 침식을 확인할 수 있었다. 실험후 분해한 콘크리트 반응시편의 단면은 침식으로 인해 매우 불규칙한 모양을 나타내었으며, 최대침식 깊이는 24mm로 나타났다. 실험중에 발생한 가스의 성분분석 결과에서 H$_2$, $CO_2$, CO 및 $O_2$, $N_2$등의 가스가 발생된 것을 알 수 있었다.