• Title/Summary/Keyword: Xenograft Mice

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Critical diagnostic and cancer stem cell markers in neoplastic cells from canine primary and xenografted pulmonary adenocarcinoma

  • Warisraporn, Tangchang;YunHyeok, Kim;Ye-In, Oh;Byung-Woo, Lee;Hyunwook, Kim;Byungil, Yoon
    • Journal of Veterinary Science
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    • v.23 no.6
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    • pp.89.1-89.7
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    • 2022
  • It is challenging to diagnose metastatic tumors whose cellular morphology is different from the primary. We characterized canine primary pulmonary adenocarcinoma (PAC) and its xenografted tumors by histological and immunohistochemical analyses for critical diagnostic and cancer stem cell (CSC) markers. To generate a tumor xenograft model, we subsequently transplanted the tissue pieces from the PAC into athymic nude mice. Immunohistochemical examination was performed for diagnostic (TTF-1, Napsin A, and SP-A) and CSC markers (CD44 and CD133). The use of CSC markers together with diagnostic markers can improve the detection and diagnosis of canine primary and metastatic adenocarcinomas.

Curcumin Induces Apoptosis and Inhibits Growth of Human Burkitt's Lymphoma in Xenograft Mouse Model

  • Li, Zai-xin;Ouyang, Ke-qing;Jiang, Xv;Wang, Dong;Hu, Yinghe
    • Molecules and Cells
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    • v.27 no.3
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    • pp.283-289
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    • 2009
  • Curcumin, a natural compound extracted from rhizomes of curcuma Curcuma species, has been shown to possess potent anti-inflammatory, anti-tumor and anti-oxidative properties. However, the mechanism of action of the compound remains poorly understood. In this report, we have analyzed the effects of curcumin on the cell proliferation of Burkitt's lymphoma Raji cells. The results demonstrated that curcumin could effectively inhibit the growth of Raji cells in a dose- and time-dependent manner. Further studies indicated that curcumin treatment resulted in apoptosis of cells. Biochemical analysis showed that the expression of Bax, Bid and cytochrome C were up-regulated, while the expression of oncogene c-Myc was down regulated after curcumin treatment. Furthermore, poly (ADP-ribose) polymerase (PARP) cleavage was induced by the compound. Interestingly, the antiapoptotic Bcl-2 expression was not significantly changed in Raji cells after curcumin treatment. These results suggested that the mechanism of action of curcumin was to induce mitochondrial damage and therefore led to Raji cell apoptosis. We further investigated the in vivo effects of curcumin on the growth of xenograft tumors in nude mice. The results showed that curcumin could effectively inhibit tumor growth in the xenograft mouse model. The overall results showed that curcumin could suppress the growth of Burkitt's lymphoma cells in both in vitro and in vivo systems.

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.

Effect of commercial Makgeolli on tumor growth in tumor xenograft mice (종양이식 모델 쥐에서 동결건조 시판 막걸리가 종양성장에 미치는 영향)

  • Shin, Eun-Ju;Kim, JaeHo;Seong, Ki-Seung;Yum, Sung-Kwan;Hwang, Jin-Taek
    • Food Science and Preservation
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    • v.23 no.1
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    • pp.104-109
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    • 2016
  • The purpose of this study was to evaluate the inhibitory effect of commercial Makgeolli on tumor growth in human gastric adenocarcinoma cells (AGS) in a xenograft cancer model, transplanted with AGS cells. Commercial Makgeolli was first dealcoholized by evaporation and used as the test sample. We detected a significant increase in the volume and weight of tumor in nude mice (induction) that were transplanted with AGS cells. Administration of $100mg/kg{\cdot}day$ group (ML), and $500mg/kg{\cdot}day$ group (MH) dealcoholized commercial Makgeolli significantly decreased tumor growth. In this study, 5-FU $18mg/kg{\cdot}day$ was used as a positive control for tumor growth inhibition. Additionally, determination of the body weight of both the groups revealed no side effects after the administration of dealcoholized commercial Makgeolli. Using the cell culture system, we also evaluated the effect of dealcoholized commercial Makgeolli on caspase-3/7 activity in the AGS cells. Treatment with dealcoholized commercial Makgeolli increased the activation of caspase-3/7 and the apoptotic markers in AGS cells in a dose-dependent manner. Therefore, dealcoholized commercial Makgeolli can be used for cancer prevention.

Tumor Inhibition Effects and Mechanisms of Angelica sinensis and Sophorae flavescentis ait Decoction Combined with Cisplatin in Xenograft Mice

  • Yan, De-Qi;Liu, Yong-Qi;Li, Ying-Dong;Li, Dou;Cheng, Xiao-Li;Wu, Zhi-Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4609-4615
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    • 2014
  • Background: To investigate tumor inhibition effects and mechanisms of Angelica sinensis and Sophorae flavescentis ait decoction (ASSF) combined with diamine-dichloroplatinum (DDP). Materials and Methods: Bodyweight, tumor inhibition rate and q value were calculated for single ASSF or ASSF combined with DDP on H22 carcinoma xenograft KM mice. Biochemical methods for serum LDH, AST, ALT, and AKP, ELISA method for serum HIF-$1{\alpha}$, pathological assessemnt of thymus, immunohistochemistry detection of tumor tissue caspase3 and mutant p53 protein, and qRT-PCR detection of bax/ bcl-2 mRNA were applied. Results: Compared with DDP control group, the bodyweight increased in ASSF-DDP group (p<0.01). Tumor inhibition rates for DDP, ASSF, ASSF-DDP were 62.7%. 43.7% and 71.0% respectively, with a q value of 0.90. Compared with other groups, thymus of DDP control group had obvious pathological injury (p<0.01), serum LDH, AST, ALT, AKP increased significantly in DDP control group (p<0.01), while serum HIF-$1{\alpha}$ was increased in the model control group. Compared with this latter, the expression of mutant p53 protein and bcl-2 mRNA were decreased in all treatment groups (p<0.01), but there were no statistical difference between DDP control p and ASSF-DDP groups. The expression of caspase3 protein and bax mRNA was increased in all treatment groups, with statistical differences between the DDP and ASSF-DDP groups (p<0.01). Conclusions: ASSF can inhibit bodyweight decrease caused by DDP, can inhibit tumor growth synergistically with DDP mainly through increasing serum HIF-$1{\alpha}$ and pro-apoptotic molecules such as caspase 3 and bax, rather than through decreasing anti-apoptotic mutant p53 and bcl-2. ASSF can reduce DDP toxicity due to decreasing the release of LDH, AST, ALT, AKP into blood and enhancing thymus protection.

Anti-Cancer Activity of T-Type Calcium Channel Blocker In Vivo

  • Park, Hang-Ah;Jung, Soo-Yeon;Lee, So-Hyung;Kang, Han-Byul;Min, Min-Sik;Kim, Jung-Ahn;Choo, Dong-Joon;Oh, Chun-Rim;Kim, Young-Deuk;Lee, Kyung-Tae;Lee, Jae-Yeol
    • Bulletin of the Korean Chemical Society
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    • v.31 no.11
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    • pp.3353-3358
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    • 2010
  • 3,4-Dihydroquinazoline 1 as T-type calcium channel blocker was in vivo evaluated against A549 xenograft in BALB/c-nu Slc mice, which exhibited 54% tumor growth inhibition through oral administration of 8 mg/kg of body weight and was slightly less active than doxorubicin (68%). In addition, this compound was also profiled for its acute toxicity to ICR mice to afford oral $LD_{50}$ value of 1,038 mg/kg of body weight.

β-carotene regulates cancer stemness in colon cancer in vivo and in vitro

  • Lee, Kyung Eun;Kwon, Minseo;Kim, Yoo Sun;Kim, Yerin;Chung, Min Gi;Heo, Seung Chul;Kim, Yuri
    • Nutrition Research and Practice
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    • v.16 no.2
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    • pp.161-172
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    • 2022
  • BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide and has a high recurrence rate, which is associated with cancer stem cells (CSCs). β-carotene (BC) possesses antioxidant activity and several anticancer mechanisms. However, no investigation has examined its effect on colon cancer stemness. MATERIALS/METHODS: CD133+CD44+ HCT116 and CD133+CD44+ HT-29 cells were isolated and analyzed their self-renewal capacity by clonogenic and sphere formation assays. Expressions of several CSCs markers and Wnt/β-catenin signaling were examined. In addition, CD133+CD44+ HCT116 cells were subcutaneously injected in xenograft mice and analyzed the effect of BC on tumor formation, tumor volume, and CSCs markers in tumors. RESULTS: BC inhibited self-renewal capacity and CSC markers, including CD44, CD133, ALDH1A1, NOTCH1, Sox2, and β-catenin in vitro. The effects of BC on CSC markers were confirmed in primary cells isolated from human CRC tumors. BC supplementation decreased the number and size of tumors and delayed the tumor-onset time in xenograft mice injected with CD133+CD44+ HCT116 cells. The inhibitory effect of BC on CSC markers and the Wnt/β-catenin signaling pathway in tumors was confirmed in vivo as well. CONCLUSIONS: These results suggest that BC may be a potential therapeutic agent for colon cancer by targeting colon CSCs.

Sanghuangporus sanghuang extract inhibits the proliferation and invasion of lung cancer cells in vitro and in vivo

  • Weike Wang;Jiling Song;Na Lu;Jing Yan;Guanping Chen
    • Nutrition Research and Practice
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    • v.17 no.6
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    • pp.1070-1083
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    • 2023
  • BACKGROUND/OBJECTIVES: Sanghuangporus sanghuang (SS) has various medicinal effects, including anti-inflammation and anticancer activities. Despite the extensive research on SS, its molecular mechanisms of action on lung cancer are unclear. This study examined the impact of an SS alcohol extract (SAE) on lung cancer using in vitro and in vivo models. MATERIALS/METHODS: Different concentrations of SAE were used to culture lung cancer cells (A549 and H1650). A cell counting kit-8 assay was used to detect the survival ability of A549 and H1650 cells. A scratch assay and transwell cell invasion assay were used to detect the migration rate and invasive ability of SAE. Western blot analysis was used to detect the expression of B-cell lymphoma-2 (Bcl-2), Bcl2-associated X (Bax), cyclin D1, cyclin-dependent kinases 4 (CDK4), signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 (p-STAT3). Lung cancer xenograft mice were used to detect the inhibiting ability of SAE in vivo. Hematoxylin and eosin staining and immunohistochemistry were used to detect the effect of SAE on the structural changes to the tumor and the expression of Bcl-2, Bax, cyclin D1, CDK4, STAT3, and p-STAT3 in lung cancer xenograft mice. RESULTS: SAE could inhibit lung cancer proliferation significantly in vitro and in vivo without cytotoxicity. SAE suppressed the viability, migration, and invasion of lung cancer cells in a dose and time-dependent manner. The SAE treatment significantly decreased the proapoptotic Bcl-2/Bax ratio and the expression of pro-proliferative proteins Cyclin D1 and CDK4 in vitro and in vivo. Furthermore, SAE also inhibited STAT3 expression. CONCLUSIONS: SAE reduced the cell viability and suppressed cell migration and invasion in human lung cancer cells. Moreover, SAE also exhibited anti-proliferation effects in vivo. Therefore, SAE may have benefits in cancer therapy.

Anti-tumor effect of Inonotus obliquus in xenograft animals with EBV+human gastric carcinoma (Inonotus obliquus (차가버섯) 추출물의 EBV 양성 인간위암에 대한 in vivo 항종양 효능 연구)

  • Lee, Seulki;Cho, Hyosun
    • Korean Journal of Microbiology
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    • v.52 no.4
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    • pp.482-486
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    • 2016
  • Inonotus obliquus is a medicinal mushroom with a variety of biological activities. It has reported to have strong anti-cancer, antioxidant and anti-inflammatory properties. EBV+ gastric carcinoma is one of the most common EBV-associated cancers that were caused by latent EBV infection. In this study, we investigated the anti-cancer effects of ethanol extract of I. obliquus using in vivo xenograft animal models implanted with EBV+ human gastric carcinoma (SNU719). We also explored the molecular mechanisms responsible for its anti-cancer activity. The result indicated that the extract of I. obliquus had an anti-cancer effect in in vivo xenograft mice with EBV+ gastric carcinoma (SNU719). Extract of I. obliquus also showed a great effect on inducing the expression of p53, p21 and Bax in tumor tissue derived from EBV+ human gastric carcinoma, and these were correlated with increased expressions of the cleaved forms of caspase-9 and Parp. Also, I. obliquus attenuated the expression of viral proteins, BZLF-1 and LMP-2 in tumor tissue from EBV+ human gastric carcinoma.

Dealcoholized Korean Rice Wine (Makgeolli) Exerts Potent Anti-Tumor Effect in AGS Human Gastric Adenocarcinoma Cells and Tumor Xenograft Mice

  • Shin, Eun Ju;Kim, Sung Hee;Kim, Jae Ho;Ha, Jaeho;Hwang, Jin-Taek
    • Journal of Microbiology and Biotechnology
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    • v.25 no.9
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    • pp.1485-1492
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    • 2015
  • Makgeolli is a traditional wine in Korea and has been traditionally believed to exhibit health benefits. However, the inhibitory effect of dealcoholized makgeolli (MK) on cancer has never been investigated scientifically. In this study, MK exhibited an anti-angiogenic effect by inhibiting tube formation in human umbilical vein endothelial cells, without cytotoxicity. Treatment with MK reduced the proliferation of AGS human gastric adenocarcinoma cells in a dose-dependent manner and increased the sub-G1 population. Next, we evaluated whether MK could induce apoptosis in AGS cells by using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay or Annexin V method. Treatment with MK at 500 and 1,000 μg/ml increased the number of TUNEL-positive AGS cells. Under the same conditions, MK-treated (500 and 1,000 μg/ml) cells showed significant induction of early or late apoptosis, compared with untreated cells (no induction). In addition, MK also induced phosphatase and tensin homolog (PTEN) expression in AGS cells. However, p53 expression in AGS cells was not changed by MK treatment. Furthermore, MK at 500 mg/kg·d reduced the tumor size and volume in AGS tumor xenografts. Taken together, MK may be useful for the prevention of cancer cell growth.