• Toxicological Research
• /
• 제11권2호
• /
• pp.175-180
• /
• 1995

We found that bufalln, one of the prominent components of the bufadlenolides in the Chinese medicine chan'su, has the potent inhibitory effects on growth and proliferation of the cultured bovine aortlc endothelial (BAE) and human umbilical vein endothelial (HUVE) cells. All naturally-occuring bufadienolides used in this study inhibited the cell growth in a dose-dependent manner. Particularly, bufalin among the bufadienolides showed the strongest inhibitory activity for the cell growth. The order of growth inhibition by bufadienolides on BAE cells was as follows: bufalin > gamabufotalln > bufotalln > cinobufagin > cinobufotalin > resibufogenin. The $IC_50$ values (50% inhibition of cell growth) of bufalin as determined by XTT assay were the range of 1-10 nM in BAE and HUVE cells. Bufalin exhibited a higher sensitivity towards cultured bovine aortic endothelial cells than human umbilical vein endothelial cells.

• Journal of Chest Surgery
• /
• 제22권1호
• /
• pp.16-24
• /
• 1989

To investigate the effects of hydrocortisone on new-born rat cardiac endothelial cells in culture, the endothelial cells were isolated by means of enzyme-cocktail method. The cells were cultivated in Lees modified Dulbeco\ulcorner medium and 10[M or 10[M of hydrocortisone was added to the medium. The cells were harvested or coverglass and processed for thiamin pyrophosphatase reaction and Feulgen reaction. The enzymatic activities of Golgi complex, number of cells and number of large nucleated[more than tetraploid] cells were counted and discussed for their significance. The results were summarized as follows; 1. Hydrocortisone seemed to accelerate the rate of recovery of cardiac endothelial cells from isolation damage. 2. Endothelial cells treated with hydrocortisone revealed strong positive reaction to thiamine pyrophosphatase in early culture and 10 M group had stronger reaction than that of 10 AM group 3. Hydrocortisone had inhibiting effects on endothelial proliferation and the higher the concentration of the reagent was the stronger effects. 4. Hydrocortisone inhibited the appearance of large nucleate cells in endothelial cell population. 5. Hydrocortisone seemed to suppress the nuclear DNA synthesis.

• Biotechnology and Bioprocess Engineering:BBE
• /
• 제9권3호
• /
• pp.201-206
• /
• 2004

Vascular endothelial growth factor (VEGF), plays a key role in angiogenesis. Many endogenous factors can affect angiogenesis in endothelial cells. VEGF is known to be a strong migration, sprouting, survival, and proliferation factor for endothelial cells during angiogenesis in endothelial cells. Searching for novel genes involved in VEGF signaling during angiogenesis, we carried out differential display polymerase chain reaction on RNA from VEGF-stimulated human umbilical vein endothelial cells (HUVECs). In this study, follistatin (FS) differentially expressed in VEGF-treated HUVECs, compared with controls. Addition of VEGF (10ng/L) produced an approximately 11.8-fold increase of FS mRNA. F5 or VEGF produced approximately 1.8- or 2.9-fold increases, respectively, in matrix metalloproteinase-2 (MMP-2) secretion for 12h, compared to the addition of a control buffer. We suggest that VEGF may affect the angiogenic effect of HUVECs, through a combination of the direct effects of VEGF itself, and the indirect effects mediated via induction of FS in vitro.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제34권4호
• /
• pp.239-245
• /
• 2012

Purpose: Vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis and lymphangiogenesis including induction of endothelial cell proliferation, migration and capillary tube formation. E7080 (S1164, Selleck chemical, Houston, TX, USA) is a muti-targeted kinase inhibitor, which targets VEGF receptor-2, 3 (VEGFR-2, 3) and inhibits survival and proliferation of tumor cell. The purpose of this study was to determine the anti-tumor effect of E7080 on oral squamous cell carcinoma. Methods: An oral squamous cell carcinoma cell line, SCC-9 was used in this study. E7080 was applied to SCC-9 cells by 3 different concentrations (1, 5, 10 ${\mu}g/mL$). Control means no application of E7080. The cellular growth was evaluated by real-time cell electronic sensing and MTT assay. The signal transduction was evaluated by Western blotting. Results: In experimental group, SCC-9 cell proliferation was decreased and the VEGFR-3 downstream pathways were inhibited compared with control. Furthermore, increasing the concentration of E7080, the ability of E7080 to disturbance of SCC-9 cell proliferation was increased. Conclusion: Proliferation of SCC-9 cells was inhibited by E7080, which was through by inhibition of VEGFR-3 downstream pathway. In vivo study with E7080 will be required to provide therapeutic benefits in oral squamous cell carcinoma.

• Archives of Plastic Surgery
• /
• 제32권6호
• /
• pp.689-698
• /
• 2005

Many studies for verifying angiogenesis have been in progress, especially in the field of abnormal vascular proliferation to explain the pathogenesis and to develop a treatment of several diseases. In our previous experiments, endothelial cell proliferations were induced by DMH stimulation in vitro, and the 177 factors(142 up-regulated and 35 down-regulated factors) were identified. Among the up-regulated factors, 9 substances (EFEMP1, CTGF, CYR61, $ITG{\beta}1$, FHL2, SERPINE1, MYC, PTTG1 and MSH6) were selected, which were related to cell proliferation and showed high signal intensities. The RNA was isolated from HUVECs at the time of 0, 6, 12, 24 hours after the DMH treatment, and RNA of control group HUVECs was also isolated. Genetic information of selected molecules was used to make primer for each, and RT-PCR was performed to analyze both groups. In control and treatment groups, each substance presented variety of manifestation degree according to time differences. EFEMP1, CTGF, CYR61, $ITG{\beta}1$, FHL2 and MYC were related to abnormal vascular proliferation steadily and SERPINE1, PTTG1 and MSH6 were related secondarily. CTGF was related to both normal and abnormal proliferation, but it played a more significant role in abnormal proliferation from earlier stage. EFEMP1, CYR61, $ITG{\beta}1$, FHL2 and MYC were similar to CTGF, although the relation appeared lately. Further study should be performed to analyze the expressions and the interactions of growth factors, which could be utilized in the new therapeutic development.

• 생명과학회지
• /
• 제20권7호
• /
• pp.1093-1099
• /
• 2010

항암 효과와 항산화 기능을 가지는 것으로 알려진 lycopene은 심혈관에서의 기능이 현재까지 잘 알려져 있지 않다. 본 연구에서는 lycopene의 심혈관 기능을 알기 위해 혈관내피세포를 이용해 다양한 세포실험을 수행하였다. 그 결과, lycopene은 내피세포의 성장 및 이동을 촉진하였으나 세포사멸에는 영향이 없었다. 또한, 백혈구의 혈관내피세포 부착을 억제하였고 내피세포 내 신호전달물질인 MAPK들의 활성을 촉발하였다. MAPK의 활성 억제제를 이용한 신호전달기전 연구실험 결과, ERK와 p38 MAPK의 활성은 세포성장에 관여하고, JNK의 활성은 세포이동에 관여함을 확인하였다. 종합하면, lycopene은 혈관내피세포의 신호전달 물질인 MAPK들를 통해 세포성장 및 이동을 촉진시키며, LPS에 의한 THP-1의 내피세포 부착을 억제 하는 등 혈관내피세포의 다양한 생리활성을 조절한다. Lycopene의 이러한 혈관내피세포 기능들은 lycopene이 혈관질환 치료제로 응용될 가능성이 있음을 의미한다.

• KSBB Journal
• /
• 제18권1호
• /
• pp.25-29
• /
• 2003

더덕의 메탄올 추출물(CL-ex)이 혈관신생에 영향을 주는 지의 여부를 알아보기 위하여, 인간태반 정맥내피세포와 돼지 폐동맥내피세포를 이용하여 실험하였다. 실험 결과, 더덕추출물은 FGF에 의해 유도된 시험관 내 혈관신생을 억제하였다. 또한 더덕추출물은 내피세포의 DNA 합성에는 영향을 주지 않았으나, FGF에 의해 증가된 내피세포의 이동을 농도 의존적으로 강하게 억제하였고, MMPs의 분비 역시 감소시켰다. 이러한 결과에 의하면, 더덕에 함유된 혈관신생 억제 물질은 혈관내피세포의 이동 과정에 작용하여 그 효과를 나타내는 것이라 추정된다. 따라서 더덕은 그 발생과 진행이 혈관신생에 의존하고 있는 것으로 알려진 암 등의 질병 예방과 치료를 위한 유용한 식물자원으로 개발될 수 있음을 시사한다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제20권5호
• /
• pp.533-538
• /
• 2016

Angiogenesis plays an essential role in embryo development, tissue repair, inflammatory diseases, and tumor growth. In the present study, we showed that endothelial nitric oxide synthase (eNOS) regulates retinal angiogenesis. Mice that lack eNOS showed growth retardation, and retinal vessel development was significantly delayed. In addition, the number of tip cells and filopodia length were significantly reduced in mice lacking eNOS. Retinal endothelial cell proliferation was significantly blocked in mice lacking eNOS, and EMG-2-induced endothelial cell sprouting was significantly reduced in aortic vessels isolated from eNOS-deficient mice. Finally, pericyte recruitment to endothelial cells and vascular smooth muscle cell coverage to blood vessels were attenuated in mice lacking eNOS. Taken together, we suggest that the endothelial cell function and blood vessel maturation are regulated by eNOS during retinal angiogenesis.

• The Korean Journal of Physiology and Pharmacology
• /
• 제19권4호
• /
• pp.335-340
• /
• 2015

Here, we investigated the role of zerumbone, a natural cyclic sesquiterpene of Zingiber zerumbet Smith, on angiogenesis using human umbilical vein endothelial cells (HUVECs). Zerumbone inhibited HUVECs proliferation, migration and tubule formation, as well as angiogenic activity by rat aorta explants. In particular, zerumbone inhibited phosphorylation of vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1, which are key regulators of endothelial cell function and angiogenesis. In vivo matrigel plug assay in mice demonstrated significant decrease in vascularization and hemoglobin content in the plugs from zerumbone-treated mice, compared with control mice. Overall, these results suggest that zerumbone inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects.

• Journal of Acupuncture Research
• /
• 제24권5호
• /
• pp.23-32
• /
• 2007

Objectives : Angiogenesis consists of the proliferation, migration, and differentiation of endothelial cells, and angiogenic factors and matrix protein interactions modulate this process. The aim of this study was to determine whether herbs medicine(KHBJs) could induce angiogenic activity in human umbilical vein endothelial cells(HUVECs). Methods : The angiogenic activity of KHBJs were evaluated by proliferation using BrdU assay, chemotactic migration assay, tube formation assay, and measurement of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor(VEGF) in HUVECs. Also, In order to identify enhance angiogenic activity by activity guided fractionation, the angiogenic activity of fractions of KHBJs such as KHBJB or KHBJR were evaluated in vitro and in vivo Matrigel plug angiogenesis asaay. Results : About 9 KHBJs significantly increased HUVECs proliferation in a dose-dependent manner. In addition, 9 herbs medicine(KHBJs) increased migration and tube-like formation in HUVECs. Interestingly the expression of bFGF and VEGF, an angiogenesis-inducing growth factor, were dose-dependently increased by KHBJs. However, angiogenic activity of fractionated KHBJs(KHBJB or KHBJR) not enhanced more than KHBJs in HUVECs and Matrigel plug in vivo angiogenesis assay. Conclusions : 9 KHBJs significantly induces angiogenesis in in vitro and in vivo. These results suggest that 9 KHBJs potent angiogenic agents and promising drug for the induction of neovascularization.