• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1465-1470
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• 2014

Inhibitor of DNA binding 1 (Id1) plays an important role in genesis and metastatic progression of prostate cancer. We previously reported that down regulation of Id1 by small interfering RNA could inhibit the proliferation of PC3 cells and growth of its xenografted tumors. Curcumin, the active ingredient of turmeric, has shown anti-cancer properties via modulation of a number of different molecular regulators. Here we investigated whether Id1 might be involved in the anti-cancer effects of curcumin in vivo and in vitro. We firstly confirmed that curcumin inhibited cell viability in a dose-dependent fashion, and induced apoptosis in PC3 cells, associated with significant decrease in the mRNA and protein expression of Id1. Similar effects of curcumin were observed in tumors of the PC3 xenografted mouse model with introperitoneal injection of curcumin once a day for one month. Tumor growth in mice was obviously suppressed by curcumin during the period of 24 to 30 days. Both mRNA and protein levels of Id1 were significantly down-regulated in xenografted tumors. Our findings point to a novel molecular pathway for curcumin anti-cancer effects. Curcumin may be used as an Id1 inhibitor to modulate Id1 expression.

• Journal of Microbiology and Biotechnology
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• 제23권9호
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• pp.1197-1205
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• 2013

Urokinase (uPA) and its receptor (uPAR) play an important role in tumor growth and metastasis. Targeting the excessive activation of this system as well as the proliferation of the tumor vascular endothelial cell would be expected to prevent tumor neovasculature and halt the tumor development. In this regard, the amino-terminal fragment (ATF) of urokinase has been confirmed as effective to inhibit the proliferation, migration, and invasiveness of cancer cells via interrupting the interaction of uPA and uPAR. Previous studies indicated that ATF expressed in Escherichia coli was mainly contained in inclusion bodies and also lacked posttranslational modifications. In this study, the biologically active and soluble ATF was cloned and expressed in Pichia pastoris. The recombinant protein was purified to be homogenous and confirmed to be biologically active. The yield of the active ATF was about 30 mg/l of the P. pastoris culture medium. The recombinant ATF (rATF) could efficiently inhibit angiogenesis, endothelial cell migration, and tumor cell invasion in vitro. Furthermore, it could inhibit in vivo xenograft tumor growth and prolong the survival of tumor-bearing mice significantly by competing with uPA for binding to cell surfaces. Therefore, P. pastoris is a highly efficient and cost-effective expression system for large-scale production of biologically active rATFs for potential therapeutic application.

• 대한기관식도과학회지
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• 제5권2호
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• pp.119-126
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• 1999

Objectives : To analyze the effect of retinoids on the differentiation in HNSCC xenografts. Materials and Methods : RA (20mg/kg) or 13-cis-RA (60mg/kg) was orally administered once in a day for 30 days in the xenograft model we prepared using athymic nude mice with AMCHN-4 and -6. We carried out H & E staining and immunohistochemical staining with the monoclonal antibody against involucrin and cytokeratin 10. Results : Both RA and 13-cis-RA were found to suppress the differentiation of AMC-HN-4. Interestingly, RA enhanced the differentiation of AMC-HN-6, although 13-cis RA did not exhibit any effect on the differentiation. These results suggest that in vivo effect of retinoids on the HNSCC growth and differentiation might be various. Retinoids-induced P450 in AMC-HN-6 might be one of the mechanisms to explain the reason why the retinoids exhibit various functions in the HNSCC.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.1787-1790
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• 2013

This study evaluated the effects of ZD1839, an orally active, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, on nasopharyngeal carcinoma (NPC) both in vitro and in vivo. Influence of ZD1839 alone or combined with cisplatin on the NPC cell line CNE2 was detected by MTT assay with flow cytometry assessment of cell cycle distribution and apoptosis rates. Nude mice NPC xenografts were also used to evaluate the effects of ZD1839 alone or combined with cisplatin. The Student's t test evaluated statistical significance. ZD1839 alone or combined with cisplatin inhibited CNE2 cell line proliferation. ZD1839 induced CNE2 cell cycle arrest in the G1 phase, and higher concentrations induced apoptosis. Xenograft tumors were significantly smaller when treated with 200 mg/kg ZD1839, cisplatin, or cisplatin combined with 100 mg/kg ZD1839 than untreated controls. ZD1839 (200 mg/kg) alone showed good tumor inhibition effects, reduction of tumor weights, and smaller tumor volume without loss of body weight. ZD1839 (200 mg/kg) might provide a good and effective therapeutic reagent for NPC.

• Journal of Gastric Cancer
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• 제20권1호
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• pp.95-105
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• 2020

Purpose: Gastric cancer is a highly metastatic malignant tumor, often characterized by chemoresistance and high mortality. In the present study, we aimed to investigate the role of B-cell lymphoma 3 (Bcl-3) protein on cell migration and chemosensitivity of gastric cancer. Materials and Methods: The gastric cancer cell lines, AGS and NCI-N87, were used for the in vitro studies and the in vivo studies were performed using BALB/c nude mice. Western blotting, wound healing assay, Cell Counting Kit-8 assay, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to evaluate the role of Bcl-3 in gastric cancer. Results: We found that the protein expression of hypoxia (HYP)-inducible factor-1α and Bcl-3 were markedly upregulated under hypoxic conditions in both AGS and NCI-N87 cells in a time-dependent manner. Interestingly, small interfering RNA-mediated knockdown of Bcl-3 expression affected the migration and chemosensitivity of the gastric cancer cells. AGS and NCI-N87 cells transfected with si-RNA-Bcl-3 (si-Bcl-3) showed significantly reduced migratory ability and increased chemosensitivity to oxaliplatin, 5-fluorouracil, and irinotecan. In addition, si-Bcl-3 restored the autophagy induced by HYP. Further, the protective role of si-Bcl-3 on the gastric cancer cells could be reversed by the autophagy inducer, rapamycin. Importantly, the in vivo xenograft tumor experiments showed similar results. Conclusions: Our present study reveals that Bcl-3 knockdown inhibits cell migration and chemoresistance of gastric cancer cells through restoring HYP-induced autophagy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6219-6225
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• 2014

Background: Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. Materials and Methods: The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Results: Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Conclusions: Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.

• 대한한의학방제학회지
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• 제12권1호
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• pp.131-148
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• 2004

In order to evaluate the anti-tumor and synergic effect of Bojungikkeehapdaechilkitang with doxorubicin, the inhibitory concentration(IC), $IC_{50}\;and\;IC_{90}$ of single use of doxorubicin and Bojungikkeehapdaechilkitang with their concomitant treatment against 3LL(Lewis lung carcinoma) was observed using MTT(Microculture Tetrazolium test) assay. In addition, their anti-tumor effects were also observed in the xenograft nude mice models agianst to 3LL cell lines. Bojungikkeehapdaechilkitang has only mimic direct anti-tumor effect against to 3LL cell lines but they were decreased general depressed signs induced by implantation of tumor cell lines and increased the total WBC and lymphocyte numbers. So, it is considered or expected that Bojungikkeehapdaechilkitang extracts were reduced the critical toxicity of doxorubicin and shows favorable synergic effect with doxorubicin and Bojungikkeehapdaechilkitang extracts.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10825-10830
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• 2015

The present study was conducted to investigate effects and mechanisms of action of phenolic alkaloids of Menispermum dauricum (PAMD) on gastric cancer in vivo. In vitro, cell apoptosis of human gastric cancer cell line SGC-7901 was observed using fluorescence staining. In vivo, a mice model was constructed to observe tumor growth with different doses. Cell apoptosis was examined using flow cytometry and K-RAS protein expression using Western blotting. The mRNA expression of P53, BCL-2, BAX, CASPASE-3, K-RAS was examined by real-time PCR. PAMD significantly suppressed tumor growth in the xenograft model of gastric cancer in a dose-dependent manner (p<0.01). Functionally, PAMD promoted cell apoptosis of the SGC-7901 cells and significantly increased the rate of cell apoptosis of gastric tumor cells (p<0.05). Mechanically, PAMD inhibited the expression of oncogenic K-RAS both at the mRNA and protein levels. In addition, PAMD affected the mRNA expression of the cell apoptosis-related genes (P53, BCL-2, BAX, CASPASE-3). PAMD could suppress gastric tumor growth in vivo, possibly through inhibiting oncogenic K-RAS, and induce cell apoptosis possibly by targeting the cell apoptosis-related genes of P53, BCL-2, BAX, CASPASE-3.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.963-968
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• 2013

Objective: To study the effect of the antagomiR-27a inhibitor on glioblastoma cells. Methods: The miR-27a expression level in specimens of human glioblastoma and normal human brain tissues excised during decompression for traumatic brain injury was assessed using qRT-PCR; The predicted target gene of miR-27a was screened out through bioinformatics databases, and the predicted gene was verified using genetic report assays; the effect of antagomiR-27a on the invasion and proliferation of glioma cells was analyzed using MTT assays and 5-ethynyl-2'-deoxyuridine (EdU) labeling. A xenograft glioblastoma model in BALB-c nude mice was established to detect the effect of antagomiR-27a on tumour growth. Results: qRT-PCR results showed that miR-27a significantly increased in specimens from glioblastoma comparing with normal human brain tissues. Th miR-27a inhibitor significantly suppressed invasion and proliferation of glioblastoma cells. FOXO3a was verified as a new target of miR-27a by Western blotting and reporter analyzes. Tumor growth in vivo was suppressed by administration of the miR-27a inhibitor. Conclusion: MiR-27a may be up-regulated in human glioblastoma, and antagomiR-27a could inhibit the proliferation and invasion ability of glioblastoma cells.

• Food Science and Biotechnology
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• 제18권1호
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• pp.103-107
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• 2009

Three traditional Chinese medicines, Agrimonia pilosa Ledeb, Grifola umbellata (pers.) Pilat, and Gambogia, are combined to form a compound extract, AGC. In this study, the in vitro and in vivo inhibitory effects of AGC on human gastric carcinoma MGC-803 cells were demonstrated, and the molecular mechanisms underlying these effects are investigated. Our results indicate that AGC inhibited MGC-803 cell growth in a dose-dependent manner as measured by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, with an $IC_{50}$ of about $6.045{\pm}0.69{\mu}g/mL$. In vivo, AGC inhibited growth of human gastric carcinoma in xenograft tumors in nude mice, and the inhibitory rate reached 55.2% at 300 mg/kg. The pro-apoptotic activity of AGC was attributed to its ability to decrease the expression of Bcl-2 and Pro-caspase3 and increase the expression of Bax. These results demonstrate that AGC can effectively induce programmed cell death and may be a promising anti-tumor drug in human gastric carcinoma.