• Nutrition Research and Practice
• /
• 제14권2호
• /
• pp.127-133
• /
• 2020

BACKGROUND/OBJECTIVES: Non-small cell lung cancer is mostly recognized among other types of lung cancer with a poor prognosis by cause of chemotherapeutic resistance and increased metastasis. Luteolin has been found to decrease cell metastasis. However, its underlying mechanisms remain unresolved. The objective of this study was to examine the effect (and its mechanism) of luteolin on the migration and invasion of human non-small cell lung cancer A549 cells. MATERIALS/METHODS: Cell viability was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Wound healing and transwell assays were evaluated to assess migration and invasion, respectively. Western blot analysis and immunofluorescence were further performed to investigate the role of luteolin and its mechanisms of action. RESULTS: Administration with up to 40 μM luteolin showed no cytotoxic activity on lung cancer A549 cells or non-cancer MRC-5 cells. Additionally, luteolin at 20-40 μM significantly suppressed A549 cells' migration, invasion, and the formation of filopodia in a concentration-dependent manner at 24 h. This is similar with western blot analysis, which revealed diminished the phosphorylated focal adhesion kinase (pFAK), phosphorylated non-receptor tyrosine kinase (pSrc), Ras-related C3 botulinum toxin substrate 1 (Rac1), cell division control protein 42 (Cdc42), and Ras homolog gene family member A (RhoA) expression levels. CONCLUSIONS: Overall, our data indicate that luteolin plays a role in controlling lung cancer cells' migration and invasion via Src/FAK and its downstream Rac1, Cdc42, and RhoA pathways. Luteolin might be considered a promising candidate for suppressing invasion and metastasis of lung cancer cells.

• BMB Reports
• /
• 제46권11호
• /
• pp.533-538
• /
• 2013

The expression of matrix metalloproteinases (MMPs) produced by cancer cells has been associated with the high potential of metastasis in several human carcinomas, including breast cancer. Several pieces of evidence demonstrate that protein tyrosine phosphatases (PTP) have functions that promote cell migration and metastasis in breast cancer. We analyzed whether PTP inhibitor might control breast cancer invasion through MMP expression. Herein, we investigate the effect of 4-hydroxy- 3,3-dimethyl-2H benzo[g]indole-2,5(3H)-dione (BVT948), a novel PTP inhibitor, on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. The expression of MMP-9 and cell invasion increased after TPA treatment, whereas TPA-induced MMP-9 expression and cell invasion were decreased by BVT948 pretreatment. Also, BVT948 suppressed NF-${\kappa}B$ activation in TPA-treated MCF-7 cells. However, BVT948 didn't block TPA-induced AP-1 activation in MCF-7 cells. Our results suggest that the PTP inhibitor blocks breast cancer invasion via suppression of the expression of MMP-9.

• 대한두경부종양학회지
• /
• 제25권2호
• /
• pp.132-137
• /
• 2009

Purpose : For the past 10 years, the incidence of thyroid cancer has been rapidly increased in female population showing current incidence of 12,000 new thyroid cancer patients annually in Korea. Though differentiated thyroid cancer is known to show favorable prognosis and excellent long-term survival from slow growth and late distant metastasis, we re-evaluated prognostic factors of recurrence and mortality following surgical procedures based on our cases. Material and Methods : 954 Patients of DTC surgically treated at Department of Surgery, Inje University Busan Paik Hospital between 1980 and 2004 were reviewed in the aspects of the surgical procedures, clinical staging, risk factors, recurrence and their outcome through median follow-up period of 10.5 years. Results : Recurrence in remnant thyroid, cervical nodes, and distant metastasis were observed in 84 paients(8.8%), and 31 patients were confirmed to be died of locoregional recurrence of cancer and distant metasasis. Regarding the risk factors to recurrence, tumor size, extrathyroidal extension, nodal metastasis, and capsular invasion were significant predictors(p<0.05). Local recurrence and distant metastasis had no statistical signiicance according to age, sex, pathology, surgery, and lymphovascular invasion. Overall 10-year survival rate was 92.4%, but low, intermediate, and high-risk patient showed 100%, 94.4%, and 70.5% respectively. Conclusion : The significant factors influencing local recurrence and distant metastasis were tumor size, extrathyroidal exension, LN metastasis, capsular invasion. In order to improve survival rate of high-risk group, appropriate and aggressive management should be recommended.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권5호
• /
• pp.3151-3154
• /
• 2013

Introduction: Colorectal cancers are in the top of the cancer-related causes of death in the world and lymph node metastasis is accepted as the primary prognostic factor. In this study, correlations of FGF19 staining pattern with local invasion and lymph node metastasis in a series of colorectal cancers were investigated. Methods: This studyincluded 81 colorectal cancer patients who underwent surgery in our hospital with no evidence of preoperative radiological distant metastasis. Routine pathological examination of the resection material was performed in order to identify vascular, perineural and serosal infiltration, regional lymph node metastasis and the degree of differentiation. Tumor tissue samples were stained with an immunohistochemistry method for FGF 19 evaluation and the staining pattern was statistically compared with the above mentioned characteristics of the tumors. Results: The patient population consisted of 47 females and 34 males with a median age of 70 years. In 40 patients regional lymph nodes were positive and 51%, 32% and 38% had serosal, perineural and vascular invasion. While 64 cases were moderately-differentiated, 11 cases were well-differentiated and 6 poorlydifferentiated, there was no association with FGF 19 staining, including intensity. Conclusion: No evidence of significant statistically correlation was found between FGF 19 staining pattern and serosal, perineural, vascular invasion, lymph node involvement and degree of differentiation.

• Journal of Microbiology and Biotechnology
• /
• 제25권12호
• /
• pp.1997-2006
• /
• 2015

Ginsenoside Rg3 is a bioactive ginseng constituent that has been reported to have diverse pathological and physiological effects, including anti-inflammatory and anti-metastatic activities. Metastasis is one of the most important factors involved in patients with melanoma. However, the molecular mechanism underlying the anti-metastatic activities of Rg3 in malignant melanoma cancer has not been fully elucidated. In this study, we have evaluated that Rg3 effectively inhibits metastasis of B16F10 melanoma cancer cells. We found that Rg3 significantly suppresses the migration, invasion, wound healing, and colony-forming abilities of B16F10 cells in a dose-dependent manner. Mechanistically, we demonstrate that Rg3 suppresses B16F10 cell metastasis by inhibiting MMP-13 expression. These results indicate that Rg3 suppresses the metastasis of B16F10 mouse melanoma cancer cells via MMP-13 regulation. Importantly, MMP-13 downregulation may influence the migration and invasion capabilities of melanoma cells and has been correlated with melanoma progression. Therefore, Rg3 is a potential therapeutic candidate that could be used to treat patients with metastatic melanoma.

• Journal of Ginseng Research
• /
• 제43권1호
• /
• pp.68-76
• /
• 2019

Background: In colorectal cancer (CRC), 40-60% of patients develop metastasis. The epithelial-mesenchymal transition (EMT) is a pivotal and intricate process that increases the metastatic potential of CRC. The aim of this study was to investigate the effect of Korean Red Ginseng extract (RGE) on colorectal metastasis through inhibition of EMT and the metastatic abilities of CRC cells. Methods: To investigate the effect of RGE on the metastatic phenotypes of CRC cells, CT26 and HT29 cells were evaluated by using an adhesion assay, a wound-healing assay, an invasion assay, zymography, and real-time reverse transcription-polymerase chain reaction. Western-blot analysis was conducted to elucidate the molecular mechanisms of RGE, which showed an inhibitory effect on the transforming growth factor-${\beta}1$ ($TGF-{\beta}1$)-induced EMT in HT29 cells. Additionally, the antimetastatic effect of RGE was evaluated in a mouse model of lung metastasis injected with CT26 cells. Results: RGE decreased the adhesion and migration ability of the CT26 cells and TGF-${\beta}1$-treated HT29 cells. The invasion ability was also reduced by RGE treatment through the inhibition of matrix metalloproteinase-9 expression and activity. Moreover, RGE suppressed the TGF-${\beta}1$-induced EMT via TGF-${\beta}1$/Smad-signaling-mediated Snail/E-cadherin expression in HT29 cells and lung tissue in CT26 tumor-bearing mice. Conclusion: Our results demonstrated that RGE inhibited colorectal lung metastasis through a reduction in metastatic phenotypes, such as migration, invasion, and the EMT of CRC cells.

• Journal of Korean Neurosurgical Society
• /
• 제51권3호
• /
• pp.147-150
• /
• 2012

Glioblastoma multiforme(GBM) is the most aggressive intracranial tumor and it commonly spreads by direct extension and infiltration into the adjacent brain tissue and along the white matter tract. The metastatic spread of GBM outside of the central nervous system (CNS) is rare. The possible mechanisms of extraneural metastasis of the GBM have been suggested. They include the lymphatic spread, the venous invasion and the direct invasion through dura and bone. We experienced a 46-year-old man who had extraneural metastasis of the G8M on his left neck. The patient was treated with surgery for 5 times, radiotherapy and chemotherapy. He had survived 6 years since first diagnosed. Although the exact mechanism of the extraneural metastasis is not well understood, this present case shows the possibility of extraneural metastasis of the G8M, especially in patients with long survival.

• 대한두경부종양학회지
• /
• 제37권2호
• /
• pp.33-41
• /
• 2021

Background/Objectives: Extra-nodal extension (ENE) is one of the strongest prognosticators in oral cancers. Here we tried to evaluate clinicopathological factors associated with the presence of ENE. Materials & Methods: We retrospectively analyzed clinical information of 120 patients who diagnosed with oral cancer and received curative surgery at our hospital from Mar 2012 to Apr 2020. We comparatively analyzed clinicopathological factors associated with the presence of lymph node (LN) metastasis and ENE, respectively. Results: Variable factors of primary tumor characteristics such as lymphovascular invasion, perineural invasion, largest diameter of tumor, depth of invasion and maximum standardized uptake value were significantly associated with the presence of cervical LN metastasis. The largest diameter of tumor was statistically significant also in multivariate analysis for predicting the LN metastasis. Meanwhile, the association between primary tumor characteristics and the presence of ENE were not statistically significant except the primary tumor size. Importantly, factors associated with LN characteristics including the maximum diameter and number of metastatic LNs were significantly associated with ENE. Conclusion: In this study, several factors affecting cervical LN metastasis and ENE in oral cancer patients were identified. The ENE seems to be influenced by the status of the metastatic LNs, such as the number of metastatic LNs, rather than the characteristics of the primary tumor itself.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권9호
• /
• pp.3811-3816
• /
• 2015

Background: Hairy and enhancer of split 1 (Hes-1) protein is a downstream target of Notch signaling and is a basic helix-loop-helix transcriptional repressor. However, definitive evidence for a role in hepatocellular carcinoma (HCC) cells has not been reported. Here, Hes-1 was revealed to an important component of the Notch signaling cascade in HCC cell lines possessing different potential for lung metastasis. Materials and Methods: RNAi mediated by plasmid constructs was used to analyze the role of Hes-1 in MHCC-97L HCC cells by assessing proliferation, apoptosis, cell migration and matrigel invasion following transfection. Hes-1 protein expression analysis in HCC tissue was also conducted by immunohistochemistry. Results: Our studies revealed that Hes-1 was decreased in HCC cell lines with higher lung metastasis potential at both the mRNA and protein levels. Down-regulation of the Hes-1 gene in MHCC-97L cells resulted in increased cell proliferation, reduced apoptosis and increased migration and invasion. Conclusions: Hes-1 has potential prognostic value in post-surgical HCC patients and may be an independent prognostic indicator for overall survival and tumor recurrence. These findings have important implications for understanding the mechanisms by which Hes-1 participates in tumor proliferation and invasion.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권9호
• /
• pp.3667-3671
• /
• 2015

Invasion and metastasis is the major cause of tumor recurrence, difficulty for cure and low survival rate. Excavating key transcription factors, which can regulate tumor invasion and metastasis, are crucial to the development of therapeutic strategies for cancers. PU.1 is a master hematopoietic transcription factor and a vital regulator in life. Here, we report that, compared to adjacent non-cancerous tissues, expression of PU.1 mRNA in metastatic hepatocellular carcinoma (HCC), but not primary HCC, was significantly down-regulated. In addition, levels of PU.1 mRNA in metastatic hepatoma cell lines MHCC97L and MHCC97H were much lower than in non-metastatic Hep3B cells. Transwell invasion assays after PU.1 siRNA transfection showed that the invasion of hepatoma cell lines was increased markedly by PU.1 knockdown. Oppositely, overexpression of PU.1 suppressed the invasion of these cells. However, knockdown and overexpression of PU.1 did not influence proliferation. Finally, we tried to explore the potential mechanism of PU.1 suppressing hepatoma cell invasion. ChIP-qPCR analysis showed that PU.1 exhibited a high binding capacity with miR-615-5p promoter sequence. Overexpression of PU.1 caused a dramatic increase of pri-, pre- and mature miR-615-5p, as well as a marked decrease of miR-615-5p target gene IGF2. These data indicate that PU.1 inhibits invasion of human HCC through promoting miR-615-5p and suppressing IGF2. These findings improve our understanding of PU.1 regulatory roles and provided a potential target for metastatic HCC diagnosis and therapy.