• Journal of Gastric Cancer
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• v.18 no.4
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• pp.356-367
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• 2018

Purpose: Kallikrein (KLK) proteases are hormone-like signaling molecules with critical functions in different cancers. This study investigated the expression of KLK6 in gastric cancer and its potential role in the growth, migration, and invasion of gastric cancer cells. Materials and Methods: In this study, we compared protein levels of KLK6, vascular endothelial growth factor (VEGF), and matrix metallopeptidase (MMP) 9 in normal gastric epithelial and gastric cancer cell lines by western blot. Fluorescence-activated cell sorting was employed to sort 2 clones of SGC-7901 cells with distinct KLK6 expression, namely, KLK6-high ($KLK6^{high}$) and KLK6-low ($KLK6^{low}$), which were then expanded. Lastly, immunohistochemical analysis was performed to investigate KLK6 expression in gastric cancer patients. Results: The expression levels of KLK6, VEGF, and MMP 9, were significantly higher in the gastric cancer cell lines SGC-7901, BGC-823, MKN-28, and MGC-803 than in the normal gastric epithelial cell line GES-1. Compared to $KLK6^{low}$ cells, $KLK6^{high}$ cells showed enhanced viability, colony-forming ability, migration, and invasion potential in vitro. Importantly, immunohistochemical analysis of a human gastric cancer tissue cohort revealed that the staining for KLK6, VEGF, and MMP9 was markedly stronger in the cancerous tissues than in the adjacent normal tissues. KLK6 expression also correlated with that of VEGF and MMP9 expression, as well as several key clinicopathological parameters. Conclusions: Together, these results suggest an important role for KLK6 in human gastric cancer progression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.3
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• pp.466-470
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• 2011

The purpose of this study was to investigate the anti-cancer effects of Carthami Flos in some kinds of human gastric cancer cells. We used two kinds of human gastric cancer cell lines, such as AGS cells and MKN45 cells. We examined cell death by MTT assay and observed the morphological changes with Carthami Flos. Also, we showed that the combination of sub-optimal doses of Carthami Flos and cisplatin noticeably suppresses in AGS cells and doxorubicin in MKN45 cells. Furthermore, we studied the caspase 3 activity to identify the apoptosis. Therefore, our findings provide insight into unraveling the effects of Carthami Flos in human gastric cancer cells and developing therapeutic agents against gastric cancer.

• Oncology Letters
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• v.42 no.5
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• pp.1904-1914
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• 2019

Apoptosis is regarded as a therapeutic target because it is typically disturbed in human cancer. Silymarin from milk thistle (Silybum marianum) has been reported to exhibit anticancer properties via regulation of apoptosis as well as anti-inflammatory, antioxidant and hepatoprotective effects. In the present study, the effects of silymarin on the inhibition of proliferation and apoptosis were examined in human gastric cancer cells. The viability of AGS human gastric cancer cells was assessed by MTT assay. The migration of AGS cells was investigated by wound healing assay. Silymarin was revealed to significantly decrease viability and migration of AGS cells in a concentration-dependent manner. In addition, the number of apoptotic bodies and the rate of apoptosis were increased in a dose-dependent manner as determined by DAPI staining and Annexin V/propidium iodide double staining. The changes in the expression of silymarin-induced apoptosis proteins were investigated in human gastric cancer cells by western blotting analysis. Silymarin increased the expression of Bax, phosphorylated (p)-JNK and p-p38, and cleaved poly-ADP ribose polymerase, and decreased the levels of Bcl-2 and p-ERK1/2 in a concentration-dependent manner. The in vivo tumor growth inhibitory effect of silymarin was investigated. Silymarin (100 mg/kg) significantly decreased the AGS tumor volume and increased apoptosis, as assessed by the TUNEL assay, confirming its tumor-inhibitory effect. Immunohistochemical staining revealed elevated expression of p-JNK and p-p38 as well as reduced expression of p-ERK1/2 associated with silymarin-treatment. Silymarin was revealed to reduce tumor growth through inhibition of p-ERK and activation of p-p38 and p-JNK in human gastric cancer cells. These results indicated that silymarin has potential for development as a cancer therapeutic due to its growth inhibitory effects and induction of apoptosis in human gastric cancer cells.

• Herbal Formula Science
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• v.30 no.2
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• pp.59-66
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• 2022

Objectives : This study is to investigate whether Carthami flos exhibits a synergistic effect on the apoptotic effect of doxorubicin on human gastric cancer cells. Methods : We used AGS, a human gastric cancer cell line. To investigate the apoptotic efficacy of doxorubicin and Carthami flos, MTT and CCK-8 methods were used. To confirm apoptosis, cell cycle and mitochondrial membrane potential changes were confirmed. To investigate the mechanism of apoptosis, the reactive oxygen species (ROS) experiment was performed. Results : 1. Doxorubicin or Carthami flos induced cell death in the human gastric cancer cell line AGS. 2. Carthami flos showed a synergistic effect of cell death by doxorubicin. 3. The cell cycle and mitochondrial membrane potential changes revealed that cell death was apoptosis. 4. Apoptosis was related to reactive oxygen species (ROS) generation. Conclusions : This result shows the anticancer synergistic effect of Carthami flos in gastric cancer cells, and is considered to be an important basis for the development of anticancer drugs for Carthami flos.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5747-5751
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• 2013

Golgi phosphoprotein 2 (GOLPH2) is a very important biomarker in a variety of diseases. Its biological function is not clear, particularly in gastric cancer. To investigate the role of GOLPH2 in human gastric cancer, and determine its effect on the Th1 lymphocyte response, its expression and that of IL-12A were measured by real-time PCR and immunohistochemistry. The relationship between GOLPH2 and IL-12A was analysed statistically. The effect of GOLPH2 on the Th1 lymphocyte response was investigated with an in vitro co-culture system. The results showed that in human gastric cancer, the expression of GOLPH2 was significantly higher and the expression of IL-12A was lower than in normal gastric mucosal tissues, and the expression levels of GOLPH2 and IL-12A were negatively correlated. In addition, obvious down-regulation of the Th1 response was observed when lymphocytes were co-cultured with gastric cancer SGC7901 cells over-expressing GOLPH2. GOLPH2 down-regulated the expression of IL-12A, and inhibited the expression of TNF-${\alpha}$ and IFN-${\gamma}$. The results indicated that GOLPH2 down-regulates the Th1 response via suppression of IL-12A in human gastric cancer, and this might provide a target for the prevention and treatment.

• YAKHAK HOEJI
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• v.56 no.6
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• pp.358-363
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• 2012

Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine protein kinase, plays an important role in wide variety of developmental events. NLK phosphorylates T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional complex and suppresses wnt signaling pathway through inhibition of ${\beta}$-catenin/TCF complex interaction. However, the function of NLK in gastric carcinogenesis has not been investigated. In the present study, we have examined whether the NLK gene is involved in the development and/or progression of gastric cancers. NLK expression was analyzed by immunohistochemical staining in 153 advanced gastric cancer specimens. Immunhistochemical analysis showed increased expression of NLK in 91 (59.5%) out of 153 gastric cancer specimens. Statistically, there was no significant relationship between altered expression of NLK protein and clinicopathological parameters, including tumor differentiation, location, lymph node metastasis. We identified that mRNA and protein expression of NLK was significantly up-regulated in human gastric cancer tissues compare to corresponding normal gastric tissues. In addition, we found that human gastric cancer cell lines exhibited relatively high expression of NLK, as compared with normal gastric cells. The results of this study suggest that aberrant regulation of NLK may contribute to the development or progression of gastric cancers and serve as a potential biomarker for advanced gastric cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5619-5625
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• 2012

Gastric carcinoma is a leading cause of cancer death in the world and multi-drug resistance (MDR) is an essential aspect of gastric carcinoma chemotherapy failure. Recent studies have shown that integrin-linked kinase (ILK) is involved in metastasis of human tumors, expression silencing of ILK inhibiting the metastasis of several types of cultured human cancer cells. However, the role and potential mechanism of ILK to reverse the multi-drug resistance in human gastric carcinoma is not fully clear. In this report, we focused on roles of expression silencing of ILK in multi-drug resistance reversal of human gastric carcinoma SGC7901/DDP cells, including increased drug sensitivity to cisplatin, cell apoptosis rates, and intracellular accumulation of Rhodamine-123, and decreased mRNA and protein expression of multi-drug resistance gene (MDR1), multi-drug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase -${\pi}$ (GST-${\pi}$) and RhoE, and transcriptional activation of AP-1 and NF-${\kappa}B$ in ILK silenced SGC7901/DDP cells. We also found that there was a decreased level of p-Akt and p-ERK. The results indicated that ILK might be used as a potential therapeutic strategy to combat multi-drug resistance through blocking PI3K-Akt and MAPK-ERK pathways in human gastric carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5583-5586
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• 2014

Helicobacter pylori (H. pylori) infection induces apoptosis in gastric epithelial cells, and this occurrence may link to gastric carcinogenesis. However, the regulatory mechanism of H. pylori-induced apoptosis is not clear. MicroRNA-146a has been implicated as a key regulator of the immune system. This report describes our discovery of molecular mechanisms of microRNA-146a regulation of apoptosis in human gastric cancer cells. We found that overexpression of microRNA-146a by transfecting microRNA-146a mimics could significantly enhance apoptosis, and this upregulation was triggered by COX-2 inhibition. Furthermore, we found that microRNA-146a density was positively correlated with apoptosis rates in H. pylori-positive gastric cancer tissues and intratumoral microRNA-146a density was negatively correlated with lymph node metastasis among H. pylori-positive gastric cancer patients. Understanding the important roles of microRNA-146a in regulating cell apoptosis in H. pylori infected human gastric cancer cells will contribute to the development of microRNA targeted therapy in the future.

• The Korea Journal of Herbology
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• v.28 no.6
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• pp.155-160
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• 2013

Objectives : Gastric cancer is a leading cause of cancer-related deaths, worldwide. Houttuynia cordata Thunberg (H. cordata) has been used as a medicinal plants and it has an anti-cancer activity in human colorectal cancer and leukemic cancer. However, the potential anti-cancer activity and mechanisms of H. cordata for human gastric cancer cells have not been tested so far. Thus, this study examined the biological effects of H. cordata on the human gastric cancer cell line SNU-1 and AGS. Methods : Inhibition of cell proliferation and cell cycle by H. cordata was carried out by MTT assay and Muse cell cycle analysis and the expressions of protein associated with apoptosis and cell cycle regulation were investigated with Western blot analysis. Results : In MTT assay, the proliferation of SNU-1 and AGS cells was significantly inhibited by H. cordata in a time and dose dependent manner, Inhibition of cell proliferation by H. cordata was in part associated with apoptotic cell death, as shown by changes in the expression ratio of Bax to Bcl-2 by H. cordata. Also, H. cordata regulated the expression of cell cycle regulatory proteins such as pRb, cyclin D1, cyclin E, CDK4, CDK2, p21 and p15. Conclusion : The antiproliferative effect of H. cordata on SNU-1 and AGS gastric cancer cells revealed in this study suggests that H. cordata has intriguing potential as a chemopreventive or chemotherapeutic agent.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3437-3442
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• 2013

The high incidence of gastric cancer and consequent mortality pose severe threats to human health. Early screening, diagnosis and treatment are the key to improve the prognosis of the patients with gastric cancer. Gastroscopy with biopsy is an efficient method for the diagnosis of early gastric cancer, but the associated discomfort and high cost make it difficult to be a routine method for screening gastric cancer. Serum tumor marker assay is a simple and practical method for detection of gastric cancer, but it is limited by poor sensitivity and specificity. Therefore, people have been looking for novel serum markers of gastric cancer in recent years. Here we review the novel serum tumor markers of gastric cancer and their diagnostic significance, focusing on the discoveries from serum proteomics analyses and epigenetics researches.