• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2807-2812
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• 2012

The purpose of this study was to examine the effect of a Toll-like receptor 5 (TLR5) agonist, CBLB502, on the growth and radiosensitivity of A549 lung cancer cells in vivo. Expression of myeloid differentiation factor 88 (MyD88) or TLR5 was stably knocked down in human lung cancer cells (A549) using lentivirus expressing short hairpin RNA targeting human MyD88 or TLR5. Lack of MyD88 or TLR5 expression enhanced tumor growth in mouse xenografts of A549 lung cancer cells. CBLB502 inhibited the growth of A549 lung cancer cells, not A549-MyD88-KD cells in vivo in the murine xenograft model. Our results showed that the inhibition of A549 by CBLB502 in vivo was realized through regulating the expression of neutrophil recruiting cytokines and neutrophil infiltration. Finally, we found that activation of TLR5 signaling did not affect the radiosensitivity of tumors in vivo.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4615-4619
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• 2013

Background: Artesunate, extracted from Artemisia annua, has been proven to have anti-cancer potential. Allicin, diallyl thiosulfinate, the main biologically active compound derived from garlic, is also of interest in cancer treatment research. This object of this report was to document synergistic effects of artesunate combined with allicin on osteosarcoma cell lines in vitro and in vivo. Methods: After treatment with artesunate and allicin at various concentrations, the viability of osteosarcoma cells was analyzed by MTT method, with assessment of invasion and motility, colony formation and apoptosis. Western Blotting was performed to determine the expression of caspase-3/9, and activity was also detected after drug treatment. Moreover, in a nude mouse model established with orthotopic xenograft tumors, tumor weight and volume were monitored after drug administration via the intraperitoneal (i.p.) route. Results: The viability of osteosarcoma cells in the combination group was significantly decreased in a concentration and time dependent manner; moreover, invasion, motility and colony formation ability were significantly suppressed and the apoptotic rate was significantly increased through caspase-3/9 expression and activity enhancement in the combination group. Furthermore, suppression of tumor growth was evident in vivo. Conclusion: Our results indicated that artesunate and allicin in combination exert synergistic effects on osteosarcoma cell proliferation and apoptosis.

• Bulletin of the Korean Chemical Society
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• 제33권1호
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• pp.111-114
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• 2012

Androgen receptor (AR) is ligand-inducible nuclear hormone receptor which has been focused on key molecular target in growth and progression of prostate cancer. We synthesized a series of 4-aryl 2-substituted aniline-thiazole analogs and evaluated their anti-cancer activity in AR-dependent human prostate cancer LNCap cells. Among them, the compound 6 inhibited the tumor growth in LNCap-inoculated xenograft model.

• BMB Reports
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• 제54권2호
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• pp.112-117
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• 2021

Phospholipase D2 (PLD2) has been implicated in the tyrosine kinase-mediated signaling pathways, but the regulation events are yet to be identified. Herein, we demonstrate that pleckstrin homology (PH) domain of PLD2 (PLD2-PH) exerts an antitumorigenic effect via the suppression of PLD2 and focal adhesion kinase (FAK). The kinase domain of FAK interacts with PLD2-PH and induces tyrosine phosphorylation and activation of PLD2. Furthermore, PLD2 increased tyrosine phosphorylation of FAK. However, ectopic expression of the PLD2-PH competes for binding to FAK and reduces the interaction between PLD2 and FAK, thereby suppressing FAK-induced PLD activation and tyrosine phosphorylation of FAK. The PLD2-PH suppressed the migration and invasion of glioblastoma cells, as well as tumor formation in a xenograft mouse model. This study uncovers a novel role of PLD2-PH as a negative regulator of PLD2 and FAK.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제33권1호
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• pp.1-9
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• 2011

Purpose: Tumor associated angiogenesis and/or lymphangiogenesis are known to be linked by VEGFR signaling pathways. These processes are regulated by several growth factors including VEGFR-2, VEGFR-3. E7080 is an orally active inhibitor of multiple tyrosine kinases including VEGFR-2, 3. Therefore, it was proposed that E7080 may inhibit angiogenesis and lymphangiogenesis. The aim of this study was to determine the effect of E7080 in a nude mouse model of OSCC. Methods: KB cells were xenografted into the submucosal tissue of the mouth floor of athymic mice. Seven days after the xenograft, the mice were randomized into 2 groups. E7080 were administered orally to the experimental group once per day. The mice were sacrificed 3 weeks after the treatment. The tumors were examined histopathologically. Immunohistochemical assays with anti- VEGF-C, VEGFR-2, VEGFR-3, phosphorylated VEGFR-2/3 (pVEGFR-2/3), and D2-40 antibodies were then performed. Results: The transplantation of human OSCC tumor cells into the mouth floor resulted in the formation of orthotopic tumors. The experimental (E7080 treatment) group showed a slowly increased tumor volume. Moreover, immunohistochemical staining demonstrated higher levels of VEGF-C, VEGFR-2, VEGFR-3, pVEGFR-2/3 and D2-40 expression in the control group than in the experimental group. Conclusion: These results suggest that E7080 may provide therapeutic benefits in OSCC.

• Journal of Ginseng Research
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• 제39권1호
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• pp.14-21
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• 2015

Background: Colorectal cancer is a leading cause of cancer-related death, and inflammatory bowel disease is a risk factor for this malignancy. We previously reported colon cancer chemoprevention potential using American ginseng (AG) in a xenograft mice model. However, the nude mouse model is not a gut-specific colon carcinogenesis animal model. Methods: In this study, an experimental colitis and colitis-associated colorectal carcinogenesis mouse model, chemically induced by azoxymethane/dextran sodium sulfate (DSS) was established and the effects of oral AG were evaluated. The contents of representative ginseng saponins in the extract were determined. Results: AG significantly reduced experimental colitis measured by the disease activity index scores. This suppression of the experimental colitis was not only evident during DSS treatment, but also very obvious after the cessation of DSS, suggesting that the ginseng significantly promoted recovery from the colitis. Consistent with the anti-inflammation data, we showed that ginseng very significantly attenuated azoxymethane/DSS-induced colon carcinogenesis by reducing the colon tumor number and tumor load. The ginseng also effectively suppressed DSS-induced proinflammatory cytokines activation using an enzyme-linked immunosorbent assay array, in which 12 proinflammatory cytokine levels were assessed, and this effect was supported subsequently by real-time polymerase chain reaction data. Conclusion: AG, as a candidate of botanical-based colon cancer chemoprevention, should be further investigated for its potential clinical utility.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4453-4458
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• 2012

Angiogenesis plays a significant role in colorectal cancer (CRC) and cyclooxygenase-2 (COX-2) appears to be involved with multiple aspects of CRC angiogenesis. Our aim was to investigate the inhibitory effects of Tan II-A (Tanshinone II-A, Tan II-A) on tumor growth in mice, as well as alteration of expression of COX-2 and VEGF in CRC. We established the mice xenograft model of C26 CRC cell line, and injected 0.5, 1, 2mg/kg of Tan II-A and 1mg/kg of 5-FU in respectively in vivo. Then, we assayed tumor weight and volume, and evaluated microvascular density and expression of VEGF. COX-2 promoter and COX-2 plasmids were transfected into HCT-116 cells, followed by detection of COX-2 promoter activity by chemiluminescence, and detection of COX-2 mRNA expression by fluorescence quantitative PCR. Taken together, the results showed Tan II-A could inhibit tumor growth and suppress the VEGF level in vivo. HCT-116 cell experiments showed marked inhibitory effects of Tan II-A on COX-2 and VEGF in a dose-dependent manner. The results indicate that Tan II-A can effectively inhibit tumor growth and angiogenesis of human colorectal cancer via inhibiting the expression level of COX-2 and VEGF.

• 대한방사성의약품학회지
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• 제9권1호
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• pp.17-21
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• 2023

In this study, we evaluated the targeting of prostate cancer (PCa) using [¹⁸F]Florastamin in non-clinical study, for the purpose of therapeutic monitoring of [¹⁷⁷Lu]Ludotadipep, a therapeutic radiopharmaceutical for PCa, [¹⁸F]Florastamin/[¹⁷⁷Lu]Ludotadipep was co-administered to a single-individual prostate tumor bearing mouse model, mimicking clinical condition. Considering the difference in half-life of the two isotopes (¹⁸F or ¹⁷⁷Lu), image scan of whole-body autoradiography was performed at 24 or 48 h after preparation of frozen section, respectively. Then, it was confirmed whether they showed the same targeting efficiency for the area of tumor. A tumor xenograft model was prepared using PSMA-overexpressing PC3-PIP prostate cancer cells. [¹⁸F]Florastamin [111 MBq (3 mCi) in 100 µL]/¹⁷⁷Lu]Ludotadipep [3.7 MBq (100 µCi) in 100 µL] was co-administered through the tail vein, and 2 hours after administration, the mice were frozen, and after freezing for 24 hours, whole-body cryosection was performed at 24 h after freezing. Image scanning using cryosection was performed after 24 or 48 hours after freezing, respectively. In the scan image after 24 hours, tumor uptake of [¹⁸F] Florastamin/[¹⁷⁷Lu]Ludotadipep were simultaneously observed specific uptake in the tumor. In the scan image after 48 hours in the same section, signal of ¹⁸F was lost by decay of radioisotope, and specific uptake image for [¹⁷⁷Lu]Ludotadipep was observed in the tumor. Uptake of [¹⁷⁷Lu]Ludotadipep was specific to the same tumor region where [¹⁸F]Florastamin/[¹⁷⁷Lu]Ludotadipep was uptake. These results suggested that [¹⁸F]Florastamin showed the same tumor uptake efficiency to PCa as [¹⁷⁷Lu]Ludotadipep, and effective therapeutic monitoring is expected to be enable using [¹⁸F]Florastamin during [¹⁷⁷Lu]Ludotadipep therapy for PCa.

• 한국식품과학회지
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• 제50권4호
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• pp.451-456
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• 2018

본 연구는 사람유래 대장암세포가 이식된 동물모델을 사용하여 사리장의 항암효과를 확인하기 이하여 수행하였다. 사리장은 죽염과 서목태, 마늘과 유근피를 혼합 추출한 물질로써 아이소플라본을 포함하고 있으며 항염, 항산화 등의 효능이 보고된 물질이다. 이러한 사리장을 종양이 이식된 동물모델에 4주간 투여하면서 종양 크기의 변화, 종양 성장인자의 변화와 사리장의 안전성을 평가하였다. 그 결과 사리장은 종양의 크기를 감소시켰으며, 종양 성장과 관련된 ERK와 p16의 발현량을 조절함으로써 종양의 성장을 억제하는 효과를 나타냈다. 또한 사리장을 투여한 시험군에서는 체중, 장기무게, 혈청생화학적검사와 조직학적 검사에서 독성으로 인한 변화가 관찰되지 않았다. 이러한 결과는 사리장이 장기복용이 가능한 항암 보조식품의 소재로써 활용될 수 있다는 것을 의미한다고 할 수 있다.

• 대한방사성의약품학회지
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• 제2권2호
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• pp.108-112
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• 2016

Molecular imaging with the radiolabeled RGD peptides for ${\alpha}_v{\beta}_3$ integrin has been an increasing interest for tumor diagnosis and the treatment monitoring. Recently, $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$ was developed for quantification of ${\alpha}_v{\beta}_3$ integrin and its biological properties was elucidated. To better understand the molecular process in vivo, we performed the kinetic analysis for the $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$. After preparation of a radiotracer, dynamic PET images were obtained in the U87MG xenograft mice for 60 min (n = 6). Binding potential values were estimated from the 3-tissue compartment model, reference Logan and simplified reference tissue model. In the early time frame (0-20 min), the liver, kidney, intestine, urinary bladder and tumor were visualized but these uptakes were diminished as time went by. The tumors showed a good contrast at 40 min after administration. $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$ showed the 2-fold uptake in the tumor compared with that in the muscle. The parametric maps for binding values also provide the higher tumor-to-background contrast than the static images. A binding value obtained from the 3-tissue compartment model was comparable to other modeling methods. From these results, we conclude that $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$ may be a promising PET radiotracer for the evaluation of angiogenesis.