Quercetin induced cell apoptosis and altered gene expression in AGS human gastric cancer cells

The integrated stress response (ISR) pathway is essential for adaption of various stresses and is related to mitochondrion-to-nucleus communication. Mitochondrial dysfunction-induced reactive oxygen species (ROS) was demonstrated to activate general control nonderepressible 2 (GCN2)–eukaryotic translation initiation factor 2α (eIF2α)–activating transcription factor-4 (ATF4) pathway-mediated cisplatin resistance of human gastric cancer cells. However, whether or how ISR activation per se could enhance chemoresistance remains unclear. In this study, we used eIF2α phosphatase inhibitor salubrinal to activate the ISR pathway and found that salubrinal reduced susceptibility to cisplatin. Moreover, salubrinal up-regulated ATF4-modulated gene expression, and knockdown of ATF4 attenuated salubrinal-induced drug resistance, suggesting that ATF4-modulated genes contribute to the process. The ATF4-modulated genes, xCT (a cystine/glutamate anti-transporter), tribbles-related protein 3 (TRB3), heme oxygenase 1 (HO-1), and phosphoenolpyruvate carboxykinase 2 (PCK2), were associated with a poorer prognosis for gastric cancer patients. By silencing individual genes, we found that xCT, but not TRB3, HO-1, or PCK2, is responsible for salubrinal-induced cisplatin resistance. In addition, salubrinal increased intracellular glutathione (GSH) and decreased cisplatin-induced lipid peroxidation. Salubrinal-induced cisplatin resistance was attenuated by inhibition of xCT and GSH biosynthesis. In conclusion, our results suggest that ISR activation by salubrinal up-regulates ATF4-modulated gene expression, increases GSH synthesis, and decreases cisplatin-induced oxidative damage, which contribute to cisplatin resistance in gastric cancer cells.

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The Antioxidant Alpha-Lipoic Acid Inhibits Proliferation and Invasion of Human Gastric Cancer Cells via Suppression of STAT3-Mediated MUC4 Gene Expression

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/3643715 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Yu Yang ◽

Erhu Fang ◽

Jiajun Luo ◽

Hongxue Wu ◽

Yue Jiang ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Cancer Cells ◽

Human Gastric Cancer ◽

Alpha Lipoic Acid ◽

Gastric Cancer Cells ◽

Muc4 Expression ◽

Cancer Tissues ◽

Muc4 Gene ◽

Proliferation And Invasion

Background. Metastasis and invasion are the main causes of mortality in gastric cancer. To improve the treatment of gastric cancer, the development of effective and innovative antitumor agents toward invasion and proliferation is needed. Alpha-lipoic acid (ALA), a naturally occurring thiol antioxidant, showed antiproliferative and cytotoxic effects on several cancers. So it is feasible to explore whether ALA can be used to inhibit proliferation and invasion in human gastric cancer. Methods. The expression of MUC4 in human gastric cancer tissues was assayed by immunohistochemistry. Then, we performed in vitro cell proliferation and invasion analysis to explore the antitumor effect of ALA using AGS, BGC-823, and MKN-28 cells. To further explore the mechanism of ALA-mediated downregulation of MUC4, we cotransfected human gastric cancer cells with STAT3 siRNA and STAT3 overexpression construct. ChIP assays were carried out to find the relationship between MUC4 and STAT3. Results. We found that the MUC4 gene was strongly expressed in human gastric cancer tissues. Meanwhile, ALA reduced proliferation and invasion of human gastric cancer cells by suppressing MUC4 expression. We also found that STAT3 was involved in the inhibition of MUC4 by ALA. Mechanistically, ALA suppressed MUC4 expression by inhibiting STAT3 binding to the MUC4 promoter region. Conclusion. ALA inhibits both proliferation and invasion of gastric cancer cells by suppression of STAT3-mediated MUC4 gene expression.

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Stem cells with fused gene expression of cytosine deaminase and interferon-β migrate to human gastric cancer cells and result in synergistic growth inhibition for potential therapeutic use

International Journal of Oncology ◽

10.3892/ijo.2011.1288 ◽

2011 ◽

Vol 40 (4) ◽

pp. 1097-1104 ◽

Cited By ~ 32

Author(s):

KYOUNG-YOON KIM ◽

BO-RIM YI ◽

HYE-RIM LEE ◽

NAM-HEE KANG ◽

EUI-BAE JEUNG ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Stem Cells ◽

Growth Inhibition ◽

Cancer Cells ◽

Cytosine Deaminase ◽

Human Gastric Cancer ◽

Interferon Β ◽

Gastric Cancer Cells ◽

Fused Gene

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Association between endogenous gene expression and growth regulation induced by TGF-β1 in human gastric cancer cells

World Journal of Gastroenterology ◽

10.3748/wjg.v11.i1.61 ◽

2005 ◽

Vol 11 (1) ◽

pp. 61 ◽

Cited By ~ 11

Author(s):

Xue Li

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Cancer Cells ◽

Growth Regulation ◽

Human Gastric Cancer ◽

Gastric Cancer Cells ◽

Endogenous Gene ◽

Tgf Β1

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AnnexinA5 Might Suppress the Phenotype of Human Gastric Cancer Cells via ERK Pathway

Frontiers in Oncology ◽

10.3389/fonc.2021.665105 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiaojie Wang ◽

Yarui Dai ◽

Yina Zhao ◽

Meichuan Li ◽

Jialu Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Apoptosis ◽

Signal Pathway ◽

Human Gastric Cancer ◽

Gastric Cancer Cells ◽

Proliferation And Metastasis ◽

Erk Signal Pathway ◽

Apoptosis And Necrosis ◽

Cell Proliferation And Metastasis

Gastric cancer is one of the most fatal diseases around the world. However, the mechanism of the development of gastric cancer is still not clarified. In addition, the anticancer drugs have cytotoxicity with different degrees. AnnexinA5, a member of the annexin family, has a great binding ability with the membrane phospholipid in a calcium dependent manner and is involved in the development of various cancers. This study aims to explore the influence of annexinA5 on human gastric cancer cells and whether it has the potential to be an auxiliary treatment to gastric cancer. In this study, the role of annexinA5 was detected from both the endogenous and the exogenous aspects on the gastric cancer cell lines MGC-803 and MKN-45. The cells were divided into a knockdown group in which RNA interference technique was used to suppress annexinA5 expression and a protein-supplementing group in which annexinA5 protein was added in the culture supernatant. After the suppression ratio of RNA interference was determined and the IC50 of annexinA5 protein was decided respectively, the cells’ proliferation was detected by MTT assay, colony formation assay, and the expression of PCNA. FCM assay and PI staining methods were applied to test cell apoptosis and necrosis. To investigate whether ANXA5 influence cell metastasis, wound healing assay and transwell assay were employed. To further detect the mechanism of annexinA5 action, the signal pathway was examined with Western Blot method. When ANXA5 gene was knocked down, cell proliferation and metastasis were promoted, while cell apoptosis was suppressed. On the other hand, after the annexinA5 protein was applied to the gastric cancer cells, cell proliferation and metastasis were inhibited, while cell apoptosis and necrosis were promoted. AnnexinA5 played its role via ERK signal pathway. ANXA5 acted as tumor suppressor gene in the gastric cancer by suppressing ERK signal pathway and has the potentiality to be an auxiliary anticancer agent.

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