Effect of epidermal growth factor receptor status on the outcomes of patients with metastatic gastric cancer: A pilot study

Aydın, Kübra; Okutur, Sadi Kerem; Bozkurt, Mehtap; Türkmen, İlknur; Namal, Esat; Pilancı, Kezban Nur; Öztürk, Akın; Akçalı, Zafer; Dogusoy, Gulen; Demir, Osman

doi:10.3892/ol.2013.1662

Cited by 14 publications

(13 citation statements)

References 20 publications

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“…Of the HER family, EGFR expression in GC was well investigated. However, the conflicting results of EGFR expression as a prognostic marker make its detection dispensable in GC 20. Therefore, like other researchers,28 we focus this study on the expression significance of the rest of the HER members, such as HER2, HER3 and HER4.…”

Section: Discussionmentioning

confidence: 99%

Protein expression of HER2, 3, 4 in gastric cancer: correlation with clinical features and survival

Lin

et al. 2015

J Clin Pathol

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Section: Discussionmentioning

confidence: 99%

Protein expression of HER2, 3, 4 in gastric cancer: correlation with clinical features and survival

Lin

et al. 2015

J Clin Pathol

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“…Expression of a high level of EGFR has been found in various types of human cancers, including colon cancer, gastric cancer, lung cancer, breast cancer, and squamous cell carcinoma of head and neck [5], [6], [7], [8], [9], [10]. Overexpression and constitutive activation of EGFR have been associated with a poor prognosis in colon cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Combination of Gefitinib and DNA Methylation Inhibitor Decitabine Exerts Synergistic Anti-Cancer Activity in Colon Cancer Cells

et al. 2014

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Despite recent advances in the treatment of human colon cancer, the chemotherapy efficacy against colon cancer is still unsatisfactory. In the present study, effects of concomitant inhibition of the epidermal growth factor receptor (EGFR) and DNA methyltransferase were examined in human colon cancer cells. We demonstrated that decitabine (a DNA methyltransferase inhibitor) synergized with gefitinib (an EGFR inhibitor) to reduce cell viability and colony formation in SW1116 and LOVO cells. However, the combination of the two compounds displayed minimal toxicity to NCM460 cells, a normal human colon mucosal epithelial cell line. The combination was also more effective at inhibiting the AKT/mTOR/S6 kinase pathway. In addition, the combination of decitabine with gefitinib markedly inhibited colon cancer cell migration. Furthermore, gefitinib synergistically enhanced decitabine-induced cytotoxicity was primarily due to apoptosis as shown by Annexin V labeling that was attenuated by z-VAD-fmk, a pan caspase inhibitor. Concomitantly, cell apoptosis resulting from the co-treatment of gefitinib and decitabine was accompanied by induction of BAX, cleaved caspase 3 and cleaved PARP, along with reduction of Bcl-2 compared to treatment with either drug alone. Interestingly, combined treatment with these two drugs increased the expression of XIAP-associated factor 1 (XAF1) which play an important role in cell apoptosis. Moreover, small interfering RNA (siRNA) depletion of XAF1 significantly attenuated colon cancer cells apoptosis induced by the combination of the two drugs. Our findings suggested that gefitinib in combination with decitabine exerted enhanced cell apoptosis in colon cancer cells were involved in mitochondrial-mediated pathway and induction of XAF1 expression. In conclusion, based on the observations from our study, we suggested that the combined administration of these two drugs might be considered as a novel therapeutic regimen for treating colon cancer.

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“…[34][35][36] AKT signaling can promote tumor growth and invasion through regulation of the expression of PCNA and MMP-9. 37 Moreover, EGFR leads to the stimulation of the AKT pathway in carcinoma cells, thus enhancing their metastatic capacity. In the present study, our finding showed that knockdown of EGFR downregulated the expression of AKT, PCNA and MMP-9 and suppressed the bioactivities of GC cells, suggesting that EGFR may be involved in the development and progression of GC via AKT-mediated regulation of the PCNA and MMP-9 expression.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of EGFR inhibits growth and invasion of gastric cancer cells

2014

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The epidermal growth factor receptor (EGFR) is an oncogenic trans-membranous receptor, which is overexpressed in multiple human cancers. However, the role of EGFR in gastric cancer (GC) is still elusive. In this study, we aimed to investigate the expression and molecular mechanisms of EGFR in GC cells. Forty cases of GC and the corresponding adjacent non-cancerous tissues (ANCT) were collected, and the expression of EGFR was assessed using immunohistochemistry in biopsy samples. Furthermore, EGFR signaling was blocked by constructed recombinant small hairpin RNA lentiviral vector (Lv-shRAGE) used to transfect into human GC SGC-7901 cells. The expression of AKT, proliferating cell nuclear antigen (PCNA) and matrix metallopeptidase-9 (MMP-9) was detected by real-time PCR and western blotting assays. Cell proliferative activities and invasive capability were, respectively, determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) and Transwell assays. Cell apoptosis and cycle distribution were analyzed by flow cytometry. EGFR was found highly expressed in cancer tissues compared with the ANCT and correlated with lymph node metastases. Knockdown of EGFR reduced cell proliferation and invasion of GC with decreased expression of AKT, PCNA and MMP-9 and induced cell apoptosis and cycle arrest. Upregulation of EGFR expression is associated with lymph node metastases of GC, and blockade of EGFR signaling suppresses growth and invasion of GC cells through AKT pathway, suggesting that EGFR may represent a potential therapeutic target for this aggressive malignancy.

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Effect of epidermal growth factor receptor status on the outcomes of patients with metastatic gastric cancer: A pilot study

Cited by 14 publications

References 20 publications

Protein expression of HER2, 3, 4 in gastric cancer: correlation with clinical features and survival

Protein expression of HER2, 3, 4 in gastric cancer: correlation with clinical features and survival

Combination of Gefitinib and DNA Methylation Inhibitor Decitabine Exerts Synergistic Anti-Cancer Activity in Colon Cancer Cells

Knockdown of EGFR inhibits growth and invasion of gastric cancer cells

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