• BMB Reports
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• v.56 no.7
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• pp.410-415
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• 2023

Breast cancer has become the most common cancer among women worldwide. Among breast cancers, metastatic breast cancer is associated with the highest mortality rate. Twist1, one of the epithelial-mesenchymal transition-regulating transcription factors, is known to promote the intravasation of breast cancer cells into metastatic sites. Therefore, targeting Twist1 to develop anti-cancer drugs might be a valuable strategy. In this study, LY-290181 dose-dependently inhibited migration, invasion, and multicellular tumor spheroid invasion in breast cancer cell lines. These anti-cancer effects of LY-290181 were mediated through the down-regulation of Twist1 protein levels. LY-290181 inhibited extracellular signal-regulated kinase and c-Jun N-terminal kinase signaling pathways. Therefore, our findings suggest that LY-290181 may serve as a basis for future research and development of an anti-cancer agent targeting metastatic cancers.

• 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.

• Nutrition Research and Practice
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• v.14 no.2
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• pp.127-133
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• 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.

• Journal of Gastric Cancer
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• v.4 no.2
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• pp.82-88
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• 2004

Purpose: E-cadherin and CD44H have been shown to play a role in the progression and the metastasis of tumors. This study evaluated the clinical correlations between expression of E-cadherin and CD44H and various clinicopathologic factors and the value of expressions of E-cadherin and CD44H as prognostic factors in Borrmann type IV gastric cancer. Materials and Methods: In 122 patients with Borrmann type IV gastric cancer, we performed the immunohistochemical stainings for E-cadherin and CD44H. We analyzed the correlation between the expressions of E-cadherin and CD44H and lymphatic invasion, venous invasion, perineural invasion, histologic type, lymph node metastasis, depth of invasion, stage, and peritoneal dissemination, and survival. Results: There were no correlations between reduced expression of E-cadherin and CD44H and lymphatic invasion, venous invasion, perineural invasion, histologic type, lymph node metastasis, depth of invasion, and stage. However, there was a significant correlation between lymph node metastasis and the lymphatic invasion (P=0.022). There was also a significant correlation between the peritoneal dissemination and CD44H expression (P=0.005). The 5-year survival rate was correlated with CD44H expression expression (P=0.026), peritoneal dissemination (P<0.01), depth of invasion (P<0.01), lymph node metastasis (P<0.01), stage of tumor (P<0.01), and lymphatic invasion (P<0.01). There was no correlation between expression of E-cadherin and survival rate. Conclusion: The expression of CD44H and peritoneal dissemination was correlated. The expression of CD44H was an independent prognostic factor in Borrmann type IV gastric cancer. Further prospective studies with a large number of cases are required.

• International Journal of Oral Biology
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• v.44 no.2
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• pp.37-42
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• 2019

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy and an increasing global public health problem. OSCC frequently invades the jaw bone. OSCC-induced bone invasion has a significant impact on tumor stage, treatment selection, patient outcome, and quality of life. A number of studies have shown that osteoclast-mediated bone resorption is a major step in the progression of bone invasion by OSCC; however, the molecular mechanisms involved in OSCC bone invasion are not yet clear. In this review, we present the clinical types of OSCC bone invasion and summarize the role of key molecules, including proteases, cytokines, and growth factors, in the sequential process of bone invasion. A better understanding of bone invasion will facilitate the discovery of molecular targets for early detection and treatment of OSCC bone invasion.

• Journal of Yeungnam Medical Science
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• v.37 no.2
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• pp.73-78
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• 2020

Cancer incidence has been increasing steadily and is the leading cause of mortality worldwide. Gastric cancer is still most common malignancy in Korea. Cancer initiation and progression are multistep processes involving various growth factors and their ligands. Among these growth factors, we have studied hepatocyte growth factor (HGF), which is associated with cell proliferation and invasion, leading to cancer and metastasis, especially in gastric cancer. We explored the intercellular communication between HGF and other surface membrane receptors in gastric cancer cell lines. Using complimentary deoxyribonucleic acid microarray technology, we found new genes associated with HGF in the stomach cancer cell lines, NUGC-3 and MKN-28, and identified their function within the HGF pathway. The HGF/N-methyl-N'-nitroso-guanidine human osteosarcoma transforming gene (c-MET) axis interacts with several molecules including E-cadherin, urokinase plasminogen activator, KiSS-1, Jun B, and lipocalin-2. This pathway may affect cell invasion and metastasis or cell apoptosis and is therefore associated with tumorigenesis and metastasis in gastric cancer.

• Journal of Gastric Cancer
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• v.20 no.2
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• pp.165-175
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• 2020

Purpose: The guidelines for pathological evaluation of early gastric cancer (EGC) recommend wider section intervals for surgical specimens (5-7 mm) than those for endoscopically resected specimens (2-3 mm). Studies in surgically resected EGC specimens showed not negligible lymph node metastasis risks in EGCs meeting the expanded criteria for endoscopic submucosal dissection (ESD). Materials and Methods: This retrospective study included 401 EGC lesions with an endoscopic size of ≤ 30 mm detected in 386 patients. Pathological specimens obtained by ESD or surgery were cut into 2-mm section intervals for reference. Submucosal or lymphovascular invasion (LVI) was evaluated arbitrarily in 4- or 6-mm section intervals. McNemar's tests compared the differences between submucosal and LVI. Results: Submucosal invasion was detected in 29.2% (117/401) and LVI in 9.5% (38/401) at 2-mm interval. The submucosal invasion detection rates in 4-mm intervals decreased to 88.0% or 90.6% (both P<0.001), while the LVI detection rates decreased to 86.8% or 57.9% (P=0.025 and P<0.001, respectively). In 6-mm intervals, the submucosal and LVI detection rates decreased further to 72.7-80.3% (P<0.001 for all three sets) and 55.3-63.2% (P<0.001 for all three sets), respectively. Among 150 out-of-indication cases at 2-mm interval, 4-10 (2.7%-6.7%) at 4-mm intervals, and 10-17 (6.7%-11.3%) at 6-mm intervals were misclassified as lesions meeting the curative resection criteria due to the underestimation of submucosal or LVI. Conclusions: After ESD, the 2-mm wide section interval was suitable for the pathological evaluation of focal submucosal or LVI. Thus, if an EGC lesion meets the expanded criteria for the ESD specimen pathological evaluation, it could be safely followed up.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6511-6517
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• 2014

Purpose: We aimed to study the relationship between thrombocytosis and clinical features of gastric cancerfocussing on platelet counts and gastric cancer progression through different TNM stages. Methods: According to the normal range of platelet count in our institution, 1,596 patients were divided to two groups: a thrombocytosis group (120 patients, > $400{\times}1000/{\mu}L$) and a control group (1,476 patients, ${\leq}400{\times}1000/{\mu}L$). Results: The incidence of thrombocytosis was 7.5%. Higher platelet counts were observed in patients with older age, larger tumor size, deeper invasion, lymph node metastasis, distant metastasis and advanced TNM stage. In multivariate logistic regression, tumor size, depth of tumor invasion, lymph node metastasis and TNM stage were independent risk factors for thrombocytosis of gastric cancer patients. On prognostic analysis, age, tumor size, tumor location, histologic type, depth of tumor invasion, lymph node metastasis, distant metastasis and TNM stage and platelet count were important factors. Tumor size, invasion depth, lymph node metastasis, TNM stage and the platelet count were independent prognostic factors. Conclusion: Thrombocytosis is associated with clinical features of gastric cancer patients and correlates with a poor prognosis.

• Journal of dental hygiene science
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• v.19 no.2
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• pp.141-146
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• 2019

Background: Oral cancer has a high incidence worldwide and has been closely associated with smoking, alcohol, and infection by the human papillomavirus. Metastasis is highly important for oral cancer survival. Lysophosphatidic acid (LPA) is a bioactive lipid mediator that promotes various cellular processes, including cell survival, proliferation, metastasis, and invasion. Signal transducer and activator of transcription (STATs) are transcription factors that mediate gene expression. Among the seven types of STATs in mammals, STAT3 is involved in invasion and metastasis of numerous tumors. However, little is known about the role of STAT3 in oral tumor invasion. In the present study, we hypothesized that STAT3 mediates LPA-induced oral cancer invasion. Methods: Immunoblotting was performed to analyze LPA-induced STAT3 activation. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was performed to assess the survival rates of YD-10B cells. STAT3 levels in LPA-treated oral tumor cells were evaluated by performing in vitro invasion assay. Results: To the best of our knowledge, this is the first study to demonstrate that LPA enhances STAT3 phosphorylation in oral cancer. In addition, treatment with WP1066, a selective inhibitor of STAT3, at a concentration that does not cause severe reduction in cell viability, significantly attenuated LPA-induced YD-10B cancer cell invasion. Conclusion: The results suggested that LPA induces oral tumor cells with greater invasive potential via STAT3 activation. Our findings provided important insights into the mechanisms underlying mouth neoplasms.

• Radiation Oncology Journal
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• v.33 no.4
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• pp.328-336
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• 2015

Purpose: Past studies have reported that S-allylcysteine (SAC) inhibits the migration and invasion of cancer cells through the restoration of E-cadherin, the reduction of matrix metalloproteinase (MMP) and Slug protein expression, and inhibition of the production of reactive oxygen species (ROS). Furthermore, evidence is emerging that shows that ROS induced by radiation could increase Met activation. Following on these reports of SAC and Met, we investigated whether SAC could suppress Met activation. Materials and Methods: Wound healing, invasion, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT), soft agar colony forming, western blotting, and gelatin zymography assays were performed in the human nasopharyngeal cancer cell lines HNE1 and HONE1 treated with SAC (0, 10, 20, or 40 mM) and hepatocyte growth factor (HGF). Results: This study showed that SAC could suppress the migration and invasion of HNE1 and HONE1 cell lines by inhibiting p-Met. An increase of migration and invasion induced by HGF and its decrease in a dose dependent manner by SAC in wound healing and invasion assays was observed. The reduction of p-Met by SAC was positively correlated with p-focal adhesion kinase (p-FAK) and p-extracellular related kinase (p-ERK in both cell lines). SAC reduced Slug, MMP2, and MMP9 involved in migration and invasion with the inhibition of Met-FAK signaling. Conclusion: These results suggest that SAC inhibited not only Met activation but also the downstream FAK, Slug, and MMP expression. Finally, SAC may be a potent anticancer compound for nasopharyngeal cancer treated with radiotherapy.