STAT3 expression in gastric cancer indicates a poor prognosis

Kim, Dae-Young; Cha, Sung-Tae; Ahn, Dae-Ho; Kang, Hae-Yoon; Kwon, C. Stephan; Ko, Ki Seong; Hwang, Seong-Gyu; Park, Pil-Won; Rim, Kyu-Sung; Hong, Sungpyo

doi:10.1111/j.1440-1746.2008.05671.x

Cited by 111 publications

(89 citation statements)

References 28 publications

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“…To address such a possibility, we examined the inhibitory effect of niditine chloride on STAT3 in 2 human gastric cancer cell lines, SGC-7901 and AGS, which are known to express constitutively active STAT3 protein (31,32). As expected, nitidine chloride blocked STAT3 phosphorylation in SGC-7901 cancer cells in dose-and time-dependent manners in both whole-cell lysate (Fig.…”

Section: Nitidine Chloride Suppresses Stat3 Signaling In Gastric Cancmentioning

confidence: 99%

Inhibition of STAT3 Signaling Pathway by Nitidine Chloride Suppressed the Angiogenesis and Growth of Human Gastric Cancer

Chen

Wang

Lin

et al. 2012

Molecular Cancer Therapeutics

139

122

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STAT3 has been strongly implicated in human malignancies, and constitutive activation of STAT3 serves a crucial role in cell survival, angiogenesis, immune evasion, and inflammation. In this study, we showed that nitidine chloride, a natural phytochemical alkaloid derived from Zanthoxylum nitidum (Roxb) DC, exerts potent anticancer activity through STAT3 signaling cascade. Nitidine chloride dose dependently suppressed VEGFinduced endothelial cell proliferation, migration, and tubular structure formation in vitro and dramatically reduced VEGF-triggered neovascularization in mouse cornea and Matrigel plugs in vivo. This angiogenesis inhibition mediated by nitidine chloride was well interpreted by the suppression of Janus kinase 2/STAT3 signaling and STAT3 DNA-binding activity in endothelial cells. Furthermore, nitidine chloride suppressed the constitutively activated STAT3 protein, its DNA-binding activity, and the expression of STAT3-dependent target genes, including cyclin D1, Bcl-xL, and VEGF in human gastric cancer cells. Consistent with the earlier findings, nitidine chloride inhibited gastric tumor cell growth and induced tumor cell apoptosis in vitro and effectively suppressed the volume, weight, and microvessel density of human SGC-7901 gastric solid tumors (n ¼ 8) at a dosage of 7 mg/kg/d (intraperitoneal injection). Immunohistochemistry and Western blot analysis further revealed that the expression of STAT3, CD31, and VEGF protein in xenografts was remarkably decreased by the alkaloid. Taken together, we propose that nitidine chloride is a promising anticancer drug candidate as a potent STAT3 signaling inhibitor. Mol Cancer Ther; 11(2); 277-87. Ó2011 AACR.

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Section: Nitidine Chloride Suppresses Stat3 Signaling In Gastric Cancmentioning

confidence: 99%

Inhibition of STAT3 Signaling Pathway by Nitidine Chloride Suppressed the Angiogenesis and Growth of Human Gastric Cancer

Chen

Wang

Lin

et al. 2012

Molecular Cancer Therapeutics

139

122

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“…Because p-STAT3 was recently shown to be a poor prognostic indicator for GC [42][43][44] its expression was evaluated in malignant versus normal tissues to determine its association with RON expression and activation. p-STAT3 extensity and intensity progressively increased from preneoplastic to neoplastic tissues; it was not present in adjacent normal tissues, but was associated with RON and MET high expression (Figs.…”

Section: Ron-msp and Met-hgf Expression In Gec Tissues And Cell Linesmentioning

confidence: 99%

RON(MST1R)is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma

Catenacci

Cervantes

Yala

et al. 2011

Cancer Biology & Therapy

107

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“…P-STAT3 and VEGF in expression of p-STAT3 and VEGF A malignancies, including gastric cancer [25,26] , to the best of our knowledge, this is the first report to show that p-STAT3 is also persistently activated in the progression of chronic gastritis to gastric carcinoma induced by MNNG in rats, and was positively associated with the expression of VEGF.…”

Section: Discussionmentioning

confidence: 98%

“…The animals were housed in groups of five per cage under controlled illumination (12:12 h light/ dark cycle, lights on/off: 6 h/18 h), humidity (60%) and temperature (22 ℃ ± 2 ℃) for one week to acclimatize to the environment. The animals were then randomly divided into two groups (60 in each group): Control group (the rats were able to eat regular food and drinking water) and the model group (the rats were able to eat regular food and drinking water containing 100 μg/mL MNNG); each group was then randomly divided into three groups (20 rats in each group): C/M15, C/ M25 and C/M40 (15,25 and 40 represent the number of feeding weeks). The Animal Care and Use Committee of the Zhejiang Chinese Medical University approved the protocol.…”

Section: Animal Preparationmentioning

confidence: 99%

Expression of p-STAT3 and vascular endothelial growth factor in MNNG-induced precancerous lesions and gastric tumors in rats

Wang¹,

Wang²,

Zheng³

et al. 2016

WJGO

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Author contributions: Wang XY and Wang LL are co-first authors; they contributed equally to the work; Zheng X, Meng LN, Lyu B and Jin HF contributed to the conception and design of the study, acquisition, analysis and interpretation of data; all authors drafted the article and made critical revisions related to the intellectual content of the manuscript, and approved the final version of the article to be published.Institutional animal care and use committee statement: The Animal Care and Use Committee of the First Affiliated Hospital of Zhejiang Chinese Medicine University approved the protocol. Conflict-of-interest statement:To the best of our knowledge, no conflict of interest exists. METHODS:One hundred and twenty Wistar rats were randomly divided into two groups (60 in each group): Control group and Model group. The rats in each group were then randomly divided into three groups (20 in each group): C/M15, C/M25 and C/M40 (15, 25 and 40 represent the number of feeding weeks from termination). Rats in the control group received normal drinking water and rats in the model group received drinking water containing 100 μg/mL MNNG. Stomach tissues were collected at the end of the 15 th , 25 th and 40 th week, respectively, for microscopic measurement using hematoxylin and eosin staining. The expression of p-STAT3 and VEGF in different pathological types of gastric tissue, including normal, inflammation, atrophy, hyperplasia and gastric stromal tumor, was observed by immunohistochemistry and Western blot, and the corelation between p-STAT3 and VEGF was analyzed. RESULTS:(1) The expression of p-STAT3 in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor were significantly increased in the model group compared with the control group (2.5 ± 1.0, 2.75 ± Wang XY et al . 6.2 ± 0.45, 5.67 ± 0.55 vs 0.75 ± 0.36, P = 0.026, 0.035, 0.001, 0.002, respectively); the expression of p-STAT3 in tissue with dysplasia was higher than that in samples with gastritis or atrophy (6.2 ± 0.45 vs 2.5 ± 1.0, P = 0.006; 6.2 ± 0.45 vs 2.75 ± 0.36, P = 0.005, respectively); however, the expression of p-STAT3 in gastritis and atrophy was not significantly different (P > 0.05); (2) the expression of VEGF in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor was significantly increased in the model group compared with normal gastric mucosa; and the expression of VEGF in tissue with dysplasia was higher than that in tissue with inflammation and atrophy (10.8 ± 1.96 vs 7.62 ± 0.25, P = 0.029; 10.8 ± 1.96 vs 6.26 ± 0.76, P = 0.033, respectively); similarly, the expression of VEGF in tissue with gastritis and atrophy was not significantly different (P > 0.05); and (3) the expression of VEGF was positively correlated with p-STAT3.CONCLUSION: p-STAT3 plays an important role in gastric cancer formation by regulating the expression of VEGF to promote the progression of gastric tumor from gastritis.

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STAT3 expression in gastric cancer indicates a poor prognosis

Abstract: We anticipate that STAT3 may be used as a molecular staging biomarker predicting poor prognosis of gastric cancer.

Cited by 111 publications

References 28 publications

Inhibition of STAT3 Signaling Pathway by Nitidine Chloride Suppressed the Angiogenesis and Growth of Human Gastric Cancer

Inhibition of STAT3 Signaling Pathway by Nitidine Chloride Suppressed the Angiogenesis and Growth of Human Gastric Cancer

RON(MST1R)is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma

Expression of p-STAT3 and vascular endothelial growth factor in MNNG-induced precancerous lesions and gastric tumors in rats

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