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Loquat (Eriobotrya japonica) leaf extract inhibits the growth of MDA-MB-231 tumors in nude mouse xenografts and invasion of MDA-MB-231 cells

  • You, Mi-Kyoung;Kim, Min-Sook;Jeong, Kyu-Shik;Kim, Eun;Kim, Yong-Jae;Kim, Hyeon-A
    • Nutrition Research and Practice
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    • v.10 no.2
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    • pp.139-147
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    • 2016
  • BACKGROUND/OBJECFTIVES: The present study was conducted to examine the inhibitory effect of loquat leaves on MDA-MB-231 cell proliferation and invasion. MATERIALS/METHODS: Female athymic nude mice were given a subcutaneous (s.c.) inoculation of MDA-MB-231 cells and randomly grouped to receive a s.c. injection of either 500 mg/kg ethanol, water extract or vehicle five times a week. Tumor growth, mitotic rate and necrosis were examined. MDA-MB-231 cells were cultured with DMSO or with various concentrations of loquat water or ethanol extract. Proliferation, adhesion, migration, invasion and matrix metalloproteinase (MMP) activity were examined. RESULTS: Tumor growth of xenograft nude mouse was significantly reduced by loquat extracts. The results of mitotic examination revealed that loquat extracts reduced tumor cell division. Both ethanol and water extracts significantly inhibited MDA-MB-231 cell proliferation. The protein expression of ErbB3 was significantly down-regulated by loquat leaf extracts. Loquat leaf extracts increased apoptosis of MDA-MB-231 cells following 24 hour incubation and the ethanol extract was more potent in inducing apoptosis than the water extract. Furthermore, loquat extracts inhibited adhesion, migration and invasion of MDA-MB-231 cells. MMP activity was significantly inhibited by loquat extracts. CONCLUSION: Our results show that extracts of loquat inhibit the growth of tumor in MDA-MB-231 xenograft nude mice and the invasion of human breast cancer cells, indicating the inhibition of tumor cell proliferation and invasion.

Safety Assessment of Ovarian Cryopreservation and Transplantation in Nude Mice Bearing Human Epithelial Ovarian Cancer

  • Zhu, Gen-Hai;Wang, Sheng-Tan;Yang, Zhao-Xin;Cai, Jun-Hong;Chen, Chun-Ying;Yao, Mao-Zhong;Hong, Lan;He, Guo-Li;Yang, Shu-Ying
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4669-4675
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    • 2012
  • Objective: Nude mice with orthotopic transplantation of human ovarian epithelial cancer were used to investigate screening criteria for paraneoplastic normal ovarian tissue and the security of the freezing and thawing for ovarian tissue transplantation. Methods: Expression of CK-7, CA125, P53, survivin, MMP-2/TIMP-2 in paraneoplastic normal ovarian tissues were detected by RT-PCR as well as immunohistochemistry. The tissues of the groups with all negative indicators of RT-PCR, all negative indicators of immunohistochemistry, negative expression of CK-7, CA125 and survivin, positive expression of CK-7, CA125 and survivin, cancer tissues and normal ovarian tissues of nude mice were used for freezing and thawing transplantation, to analyze overt and occult carcinogenesis rates after transplantation. Results: When all indicators or the main indicators, CK-7, CA125 and survivin, were negative, tumorigenesis did not occur after transplantation. In addition the occult carcinogenesis rate was lower than in the group with positive expression of CK-7, CA125 and survivin (P<0.01). After subcutaneous and orthotopic transplantation of ovarian tissues, rates did not change (P>0.05). There was no statistical significance among rates after transplantation of ovarian tissues which were obtained under different severity conditions (P>0.05). Conclusion: Negative expression of CK-7, CA125 and survivin can be treated as screening criteria for security of ovarian tissues for transplantation. Immunohistochemical methods can be used as the primary detection approach. Both subcutaneous and orthotopic transplantation are safe. The initial severity does not affect the carcinogenesis rate after tissue transplantation. Freezing and thawing ovarian tissue transplantation in nude mice with human epithelial ovarian carcinoma is feasible and safe.

Anti-tumorigenic and Invasive Activity of Colon Cancer Cells Transfected with the Retroviral Vector Encoding Tissue Inhibitor of Metalloproteinase-2 (레트로바이러스를 이용한 Tissue Inhibitor of Metalloproteinase-2 유전자 발현이 대장암 세포의 전이 및 종양형성에 미치는 영향)

  • 오일웅;정자영;장석기;이수해;김연수;손여원
    • YAKHAK HOEJI
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    • v.48 no.3
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    • pp.189-196
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    • 2004
  • Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) playa key role in tumor invasion and metastasis. As an inhibitor of MMP-2, TIMP-2 is known to block both the invasive and metastatic behavior of cancer cells, and decrease tumor growth activity. We performed this study to investigate the effects of TIMP-2 over-expression induced by retroviral mediated gene transfer in vitro and in vivo. The human colon cancer cell line SW480 was transfected with the retroviral vector encoding TIMP-2. The effects of TIMP-2 over-expression were analyzed by invasion assay and gelatinase activity test in colon cancer cells and tumorigencity in nude mice. In evaluation of the transfection efficiency of the retroviral vector encoding TIMP-2 in colon cancer cells, we confirmed up-regulation of TIMP-2 expression dependent on the time of cell culture. In addition, inhibition of MMP-2 expression in SW480/TIMP-2 was shown by gelatin zymography. In the in vitro invasion assay SW480/TIMP-2 inhibited the invasiveness on matrigel coated with collagen. To determine whether TIMP-2 can modulate in vivo tumorigenicity and metastasis, SW480/TIMP-2 cells were injected subcutaneously in nude mice. The tumor mass formation of SW480/TIMP-2 cells in nude mice was markedly decreased compared to nontransfected cancer cells. These results showed that colon cancer cells transfected with the retroviral vector encoding TIMP-2 inhibits the invasiveness in vitro and tumorigenicity in vivo.

Inhibitory Effects of 3-Bromopyruvate on Human Gastric Cancer Implant Tumors in Nude Mice

  • Xian, Shu-Lin;Cao, Wei;Zhang, Xiao-Dong;Lu, Yun-Fei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3175-3178
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    • 2014
  • Background: Gastric cancer is a common malignant tumor. Our previous study demonstrated inhibitory effects of 3-bromopyruvate (3-BrPA) on pleural mesothelioma. Moreover, we found that 3-BrPA could inhibit human gastric cancer cell line SGC-7901 proliferation in vitro, but whether similar effects might be exerted in vivo have remained unclear. Aim: To investigate the effect of 3-BrPA to human gastric cancer implant tumors in nude mice. Materials and Methods: Animals were randomly divided into 6 groups: 3-BrPA low, medium and high dose groups, PBS negative control group 1 (PH7.4), control group 2 (PH 6.8-7.8) and positive control group receiving 5-FU. The TUNEL method was used to detect apoptosis, and cell morphology and structural changes of tumor tissue were observed under transmission electron microscopy (TEM). Results: 3-BrPA low, medium, high dose group, and 5-FU group, the tumor volume inhibition rates were 34.5%, 40.2%, 45.1%, 47.3%, tumor volume of experimental group compared with 2 PBS groups (p<0.05), with no significant difference between the high dose and 5-FU groups (p>0.05). TEM showed typical characteristics of apoptosis. TUNEL demonstrated apoptosis indices of 28.7%, 39.7%, 48.7% for the 3-BrPA low, medium, high dose groups, 42.2% for the 5-FU group and 5% and 4.3% for the PBS1 (PH7.4) and PBS2 (PH6.8-7.8) groups. Compared each experimental group with 2 negative control groups, there was significant difference (p<0.05); there was no significant difference between 5-FU group and medium dose group (p>0.05), but there was between the 5-FU and high dose groups (p<0.05). Conclusions: This study indicated that 3-BrPA in vivo has strong inhibitory effects on human gastric cancer implant tumors in nude mice.

AN EXPERIMENTAL STUDY FOR ESTABLISHMENT OF ORTHOTOPIC SALIVARY TUMOR MODELS IN MICE (마우스에서 타액선암 동위종양 모델 제작을 위한 실험적 연구)

  • Park, Young-Wook;Chung, Seong-Hoon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.33 no.2
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    • pp.81-93
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    • 2007
  • Purpose: Adenoid cystic carcinoma (ACC) is a relatively rare tumor that arises in glandular tissues of the head and neck region and sometimes has a protracted clinical course with perineural invasion and delayed onset of distant lung metastasis. Treatment failure of salivary ACC is most often associated with perineural and hematogenous tumor spread. However, very little has been known about the cellular and molecular mechanisms of perineural invasion and hematogenous distant metastasis of parotid ACC. This study was designed to develop an orthotopic tumor model of parotid adenoid cystic carcinoma in athymic nude mice. Experimental Design: A melanoma cell line was injected into the parotid gland of athymic mice to determine whether such implantation was technically feasible. A parotid ACC cell line was then injected into the parotid gland or the subcutaneous tissue of athymic mice at various concentrations of tumor cells, and the mice were thereafter followed for development of tumor nodule. The tumors were examined histopathologically for perineural invasion or regional or distant lung metastasis. We used an oral squmous cell carcinoma cell line as control. Results: Implantation of tumor(melanoma) cell suspension into the parotid gland of nude mice was technically feasible and resulted in the formation of parotid tumors. A parotid ACC cell line, ACC3 showed no significantly higher tumorigenicity, but showed significantly higher lung metastatic potential in the parotid gland than in the subcutis. In contrast, mucosal squmous cell carcinoma cell line doesn’t show significantly higher lung metastatic potential in the parotid gland than in the subcutis. The ACC tumor established in the parotid gland seemed to demonstrate perineural invasion of facial nerve, needs further study. Conclusion: An orthotopic tumor model of salivary ACC in athymic nude mice was successfully developed that closely recapitulates the clinical situations of human salivary ACC. This model should facilitate the understanding of the cellular and molecular mechanisms of tumorigenisis and metastasis of salivary ACC and aid in the development of targeted molecular therapies of salivary ACC.

Antitumor Effect of $18{\beta}$-Glycyrrhetinic Acid against Human Tumor Xenografts Caused by A549 Cancer Cell (A549 암세포 기인성 종양에 대한 $18{\beta}$-Glycyrrhetinic Acid의 항종양효과)

  • Kim, Ha-Yan;Kim, Song-Yi;Lee, Jue-Hee;Han, Yong-Moon
    • YAKHAK HOEJI
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    • v.55 no.1
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    • pp.39-44
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    • 2011
  • Many reports indicate that $18{\beta}$-glycyrrhetinic acid ($18{\beta}$-GA) from Glycyrrhizae Radix has anti-inflammatory and immunoregulatory activities, whereas reports regarding anticancer activity of the compound are few. In present study, we investigated antitumor effect of $18{\beta}$-GA on tumor caused by A549 cancer cell in mice. Data resulting from the cytotoxicity assay showed that $18{\beta}$-GA caused killing of A549 cells. $LD_{50}$ values of $18{\beta}$-GA were app. 180 ${\mu}M$ and 80 ${\mu}M$, corresponding to 48 hr- and 72 hr-treatments, displaying that the killing activity was more effective as the $18{\beta}$-GA treatment was prolonged. Based on these data, antitumor effect of $18{\beta}$-GA was tested in nude mice. For induction of the tumor, A549 ($3{\times}10^6$ cells/mouse) was injected subcutaneously into the lateral abdomen of nude mice (Balb/c nu/nu). To determine the antitumor effect, nude mice with tumor were given $18{\beta}$-GA (1 mg/200 ${\mu}l$/mouse) intraperitoneally every three days for four times. Tumor-sizes were measured with a caliper for a period of 24 days. Results showed that the $18{\beta}$-GA treatment reduced the tumor-sizes (P<0.05) as compared with negative control nude mice that received diluent (DPBS). The reduction degree was greater than reduction degree by doxorubicin (60 ${\mu}g$/mouse), and the pattern of reduction was almost sustained during the entire period of the observation. In conclusion, our studies demonstrate that $18{\beta}$-GA has antitumor activity to the A549 cancer cell-caused tumor.

AN ATOPIC NUDE MOUSE MODEL OF ORAL CANCER CELL LINE (구강암 세포주의 이소위 누드마우스 종양 모델)

  • Kim, Jong-Hyun;Hwang, Young-Sun;Kim, Hyun-Sil;Nam, Woong;Cha, In-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.35 no.2
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    • pp.74-82
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    • 2009
  • In order to make successful oral cancer treatment, we need to understand about tumor biology and effective chemotherapeutic agents. To achieve these studies, it is necessary to develope a proper in-vivo model. Therefore the author will make try to develop more improved animal model of more applicable in various method of cancer study. In this study, the author induced in-vivo tumorigenesis in nude mice by $YD-10B_{mod}$ cell line used by YD-10B cell line originated from oral tongue squamous cell carcinoma and observed tumor formations and invasiveness of surrounding tissue, and found some results as follows : 1. The experimental group($YD-10B_{mod}$, subcutaneous injection) produced tumors 13 out of 15 mice, while the control group produced none of 5 mice. 2. The inoculation of $1{\times}10^6$cells/mouse produced tumors 3 out of 5 mice and inoculation of $1{\times}10^7$cells/mouse, $2{\times}10^7$cells/mouse produced tumors in every 5 mice. 3. In the histopathologic studies, the inoculation of $1{\times}10^6$cells/mouse group showed the characteristic features of well-differentiated squamous cell carcinoma and demarcated expansile growth, while the inoculation of $1{\times}10^7$cells/mouse, $2{\times}10^7$cells/mouse group showed the expansile growth with partial central necrosis and invasive growth to surrounding fat & connective tissue. These findings suggest that atopic xenograft of $YD-10B_{mod}$ cell line in nude mice has a improved productivity of tumors, produced tumors showed the characteristics feature of human tumor and invasive growth to surrounding tissue in histopathologic appearance. These atopic nude mouse model of tongue carcinoma might assist in studying oral cancer biology and effective choice of chemotherapeutic agents.

Anti-proliferation Effect of Damina 909 on Pancreatic Cancer Cells in Tumor-Xenografted Nude Mice Model

  • Kim, Yu-Ri;Lee, Seung-Min;Seo, Sang-Hui;Lee, Seung-Ho;Kim, In-Kyoung;Jun, Hwang-Jeok;Nam, Jong-Hyun;Kim, Meyoung-Kon
    • Molecular & Cellular Toxicology
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    • v.5 no.1
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    • pp.7-13
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    • 2009
  • In this study, we investigated the anti-proliferative effect of Damina 909 in human cancer cell lines and tumor-xenografted nude mice to elucidate its potential in treating many cancers. Damina 909 treatment resulted in inhibition of cell proliferation of human pancreatic cancer cells. Our in vivo study showed that the weight of pancreatic tumors in Damina 909-treated group were the lighter than control group. Consequently, the intake of food and water in Damina 909-treated group did not change, while those in control group were steadily decreased over a period of treatment. Moreover, Damina 909 treatment elevated the protein expression of p53 and p21 in pancreatic tumor of xenografted nude mice. In summary, compare to other human cancer cells such as prostate and hepatocyte, Damina 909 is most effectively inhibited proliferation of pancreatic cancer cells by increasing the expression of tumor suppressor genes. This led us to speculate that a candidate substance for effective cancer therapy of pancreatic cancer might be contained in Damina 909.

Xenografted Tumorigenesis in the oral vestibule of nude mice by Snail transfection: Histological and immunohistochemical study

  • Kim, Moon-Key;Lee, Eun-Ha;Kim, Jin;Yook, Jong-In;Cha, In-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.35 no.4
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    • pp.199-204
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    • 2009
  • Purpose: The purpose of this study is to investigate the epithelial-mesenchymal transition (EMT) induced by Snail transcription factor and Snail-transfected in vivo tumors with histopathological features. Materials and methods: We induced in vivo xenografted tumorigenesis in the oral vestibules of nude mice by a Snail transfected HaCaT cell line and investigated morphological and immunohistochemical features in Snail expressive tumors. Results: We identified tumor masses in 14 out of 15 nude mice in the HaCaT-Snail cell inoculation group, but no tumors were present in any of the HaCaT cell inoculation group. Induced tumors showed features of poorly differentiated carcinoma with invasion to neighboring muscles and bones. The HaCaT-Snail tumors showed decreased expressions of E-cadherin and cytokeratin, but showed increased expressions of vimentin and N-cadherin. Discussion: The Snail transfected xenograft can improve productivity of malignant tumors, show various histopathological features including invasive growth, and aid in the investigation of tumor progression and the interaction with surrounding tissues.

In Vivo Anti-tumor Activity of 3-Methyl-6-allylthiopyridazine in Nude Mice Xenografted with Hep-G2 Hepatocarcinoma

  • Kwon, Soon-Kyoung;Moon, Aree
    • Biomolecules & Therapeutics
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    • v.13 no.2
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    • pp.113-117
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    • 2005
  • Organosulfur compounds have been shown to exert an anti-cancer activity. In an attempt to develop novel chemopreventive and anti-cancer agents for liver cancer, we synthesized allylthiopyridazine derivatives. We have previously shown that allylthiopyridazine derivatives exert inhibitory effects on proliferation, invasion and migration of SK-Hep-1 hepatocarcinoma cells in vitro. The in vivo anti-tumor effect of 3-methvl-6-allylthiopy-ridazine, named as K6, was also reported. In this study, we further investigated the preclinical anti-cancer efficacy of K6 for hepatocarcinoma using nude mice xenografted with Hep-G2 hepatocellular carcinoma cells. K6(20-100 mg/kg, orally administered everyday for 30 days) markedly decreased the tumor volume of Hep-G2 cell-transplanted nude mice as evidenced by ultrasonographic and plethysmogranhic analyses. The inhibitory effect on tumor volume was lower than that exerted by doxorubicin (2 mg/kg), intravenously injected) which was used as a positive control. This study shows that K6 efficiently suppresses xenograft tumor growth, revealing K6 as apotential anti-cancer agent for suppressing in vivo progression of liver cancer. Given that hepatocarcinoma is among the most prevalent and lethal malignancies and there is no effective treatment to date, our study may contribute to the potential drug development for liver cancer.