Oncology Research 20(8) Abstracts

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Oncology Research, Vol. 20, pp. 333–340, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13657689382734
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Deregulation of HER2 Downstream Signaling in Breast Cancer Cells by a Cocktail of Anti-HER2 scFvs

Foroogh Nejatollahi,*† Reza Ranjbar,‡ Vahid Younesi,*†§ and Mahdi Asgharpour†§

*Shiraz HIV/AIDS Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
†Recombinant Antibody Laboratory, Department of Immunology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
‡Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
§Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 30% of patients with breast cancer. HER2 targeting is the mainstay of targeted therapy for the treatment of invasive breast cancers. Due to biological and therapeutic advantages, single chain fragment variable (scFv) antibodies have emerged as promising alternative therapeutics. In this study, we assessed the capability of three scFvs against HER2 extracellular domains (II, III, IV) in deregulation of some key signaling mediators that have important roles in growth, survival, angiogenesis, and cell migration of breast tumor cells. Downregulation of activated Akt (p-Akt), increase of p27 protein levels, and downregulation of HER1, HER2, HER3 and epidermal growth factor (EGF), CXCR3, CXCL10, and MMP2 were observed following treatment of breast cancer cells (SKBR3 cell line) with the scFvs and their combination. Our results suggest that the combination of the three scFvs could be considered as an effective cocktail on HER2 tumorgenic signaling pathways that leads to tumor growth suppression and death.

Key words: Single chain fragment variable (scFv); Targeted therapy; Human epidermal growth factor receptor 2 (HER2) signaling mediators

Address correspondence to Dr. Foroogh Nejatollahi, Associate Professor, Recombinant Antibody Laboratory, Department of Immunology, Shiraz University of Medical Sciences, P.O. Box 71345-3119, Shiraz, Iran. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 341–350, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13657689382851
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Upregulation of Glycoprotein Nonmetastatic B by Colony-Stimulating Factor-1 and Epithelial Cell Adhesion Molecule in Hepatocellular Carcinoma Cells

Feng Tian, Chang Liu, Qifei Wu, Kai Qu, Ruitao Wang, Jichao Wei, Fandi Meng, Sinan Liu, and Hulin Chang

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, Shaanxi Province, P.R. China

Considerable effort has been made in elucidating the appropriate biomarkers and the mechanism and functional significance of these biomarkers in hepatocellular carcinoma (HCC). Glycoprotein nonmetastatic B (GPNMB) overexpression occurs in cutaneous melanomas and breast cancer, and it is an attractive candidate for cancer therapy. However, little is known about the expression and regulation of GPNMB in HCC. In this study, we investigated the expression of GPNMB in HCC histochemically and tested the regulation effects of the epithelial cell adhesion molecule (EpCAM) and colony-stimulating factor (CSF-1) on the expression of GPNMB in HCC cells. Our results demonstrated that GPNMB levels were significantly enhanced in HCC compared with adjacent normal liver tissues. In HCC cells, GPNMB expression was regulated by EpCAM and CSF-1 partly through their common downstream product c-myc. Taken together, these results suggest that GPNMB, the expression of which was regulated in HCC cells by the highly coordinated function of various proteins, may be a potential target for HCC therapy.

Key words: Glycoprotein nonmetastatic B (GPNMB); Hepatocellular carcinoma (HCC); Colony-stimulating factor-1 (CSF-1); Epithelial cell adhesion molecule (EpCAM); c-myc

Address correspondence to Chang Liu, No. 277 West Yan-ta Road, Xi’an, Shaanxi Province, 710061, P.R. China. Tel: +86-029-85323900; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 351–357, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13657689382897
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Simvastatin Inhibits Proliferation and Induces Apoptosis in Human Lung Cancer Cells

Xiaofeng Yu,* Yinghua Pan,† Housheng Ma,† and Wenjun Li*

*Department of Thoracic Surgery, Yuhuangding Hospital, Yantai, Shandong, China
†Department of Radiology, Yuhuangding Hospital, Yantai, Shandong, China

Lung cancer is the one of the most frequent causes of malignant tumors. In recent years, it has been documented that statins have anticancer and cancer chemopreventive properties. However, the mechanism of simvastatin on lung cancer is still unclear. In this study, the human lung cancer cell line A549 cells were incubated with simvastatin. Simvastatin inhibited the survival of A549 cells in a dose-dependent manner, decreased Bcl-2 protein expression, and increased Bax protein expression time and dose dependently. In addition, simvastatin blocked cells in the G1 phase of the cell cycle, downregulated cyclin D1 and CDKs protein expression, mediated the mitochondria-dependent caspase cascade by increasing caspase-3, -8, and -9 mRNA and protein expression, downregulated Xiap levels to induce cells apoptosis. Importantly, simvastatin suppressed decreased MMP-9 protein expression and suppressed NF-κB activation in A549 cells. Taken together, these results showed that the anticancer effect of simvastatin in lung cancer A549 cells via the inhibiting cell proliferation, influencing the cell cycle, downregulating cyclin D1 and CDKs expression, inducing apoptosis, and decreasing MMP-9 levels, possibly by inhibiting the activation of NF-κB. Statins contribute to lung cancer therapy and may be an ideal anticancer and cancer chemopreventive agent for lung cancer.

Key words: Cancer; Statins; Apoptosis; Proliferation

Address correspondence to Wenjun Li, Department of Thoracic Surgery, Yuhuangding Hospital, Yuhuangding Road, Yantai, China. Tel: +86-0535-6691999-81842; Fax: +86-0535-6691999; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 359–368, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13657689382932
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Triptolide Induces Apoptosis and Inhibits the Growth and Angiogenesis of Human Pancreatic Cancer Cells by Downregulating COX-2 and VEGF

Jian-Xia Ma,*1 Yun-Liang Sun,†1 Yi-Qian Wang,* Hong-Yu Wu,‡ Jing Jin,‡ and Xiao-Feng Yu*

*Department of Gastroenterology, Huadong Hospital, Fudan University, Shanghai, China
†Department of Gastroenterology, The People’s Hospital of Ganyu County, Ganyu, Jiangsu, China
‡Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China

Triptolide (TPL) inhibits the growth and proliferation of a wide range of human cancer cells, but the underlying mechanism is largely unknown. Here, we report that TPL induces apoptosis and inhibits proliferation of PANC-1 pancreatic cancer cells by downregulating cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF). Cell viability and apoptosis were measured by MTT assay and flow cytometry. Real-time PCR and Western blot were used to examine the expression of COX-2 and VEGF. The Matrigel angiogenesis and Transwell migration were employed to assess tube formation and cell migration. Pancreatic cancer mouse xenografts were established to investigate the in vivo antitumor effects of TPL. TUNEL staining and immunohistochemistry were used to detect the apoptosis rate and protein expression in tumor tissues. TPL inhibited the proliferation of pancreatic cancer cells in a time and concentration-dependent manner and decreased the expression of COX-2 and VEGF in vitro. Furthermore, medium from TPL-treated PANC-1 cells inhibited the proliferation, migration, and tube formation of HUVECs. TPL significantly reduced the growth of pancreatic cancer mouse xenografts, accompanied by an induction of apoptosis, inhibition of angiogenesis, and reduction of COX-2 and VEGF. Our data indicate that suppressing the expression of COX-2 and VEGF may be one of the molecular mechanisms by which TPL induces apoptosis and inhibits the growth and angiogenesis of human pancreatic cancer cells.

Key words: Triptolide (TPL); Pancreatic cancer; Angiogenesis; Cyclooxygenase-2 (COX-2); Vascular endothelial growth factor (VEGF)

1These authors provided equal contribution to this work.
Address correspondence to Dr. Xiao-Feng Yu, Department of Gastroenterology, Huadong Hospital, Fudan University, 221 West Yan’an Road, Shanghai 200338, China. Tel: +86-0-13472876295; Fax: +86-21-53590294; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 369–376, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13657689382978
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Oldhamianoside II, a New Triterpenoid Saponin, Prevents Tumor Growth via Inducing Cell Apoptosis and Inhibiting Angiogenesis

Feng-Ling Wang,* Jing-Yong Sun,* Yan Wang,* Yan-Ling Mu,* Yu-Ji Liang,* Zhao-Zhong Chong,† San-Hai Qin,* and Qing-Qiang Yao*

*Key Laboratory for Rare Disease of Shandong Province, Department of Pharmacology, Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, China
†Laboratory of Cellular and Molecular Signaling, New Jersey Medical School, New Jersey Health Sciences University, Newark, NJ, USA

Oldhamianoside II is a new triterpenoid saponin that was isolated from the roots of Gypsophila oldhamiana. The present study aims to investigate the potential inhibitory activity of oldhamianoside II on tumor growth using an S180 tumor implantation mouse model. Oldhamianoside II at doses of 5.0 and 10.0 mg/kg was given with intraperitoneal injection for 10 days following subcutaneous inoculation of S180 tumor cells in anterior flank of mice. The tumor growth, the cell apoptosis, the microvessel density (MVD) in S180 tumors, the tumor cell viability, the tubular formation in vitro, and migration of tumor cells were examined. The expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and cyclooxygenase-2 (COX-2) was determined to analyze the associated mechanisms. The results showed that oldhamianoside II potently inhibited tumor cell viability in vitro. In addition, oldhamianoside II delayed tumor growth in anterior flank, induced S180 cell apoptosis, and reduced the MVD. Oldhamianoside II was also demonstrated to decrease the number of tubular structure and vessel formation in HUVEC cultures and chick embryo chorioallantoic membrane (CAM) model, respectively. Further study indicated that oldhamianoside II reduced the expression of VEGF, bFGF, and COX-2 in tumor sections. Moreover, oldhamianoside II inhibited the activity of migration and penetration to Matrigel of SGC7901 tumor cells in scratch wound and transwell chamber. In conclusion, our work defines oldhamianoside II, a new triterpenoid saponin, as a novel compound that can effectively inhibit S180 tumor growth, induce tumor cell apoptosis, prevent tumor angiogenesis, and inhibit cancer cell migration, suggesting that oldhamianoside II is a potential drug candidate for the treatment of cancer and for the prevention of metastasis.

Key words: Oldhamianoside II; Saponin; Apoptosis; Angiogenesis; Tumor metastasis

Address correspondence to Dr. Qing-Qiang Yao, Key Laboratory for Rare Disease of Shandong Province, Department of Pharmacology, Institute of Materia Medica, Shandong Academy of Medical Sciences, No. 18877 Jingshi Road, Jinan, 250062, Shandong, China. Tel: +86-0531-82612443; Fax: +86-0531-82612443; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 377–381, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13657689383012
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Knockdown of Pokemon Protein Expression Inhibits Hepatocellular Carcinoma Cell Proliferation by Suppression of AKT Activity

Xiaosan Zhu,*† Yichen Dai,* Zhangxin Chen,* Junpei Xie,* Wei Zeng,* and Yuanyuan Lin*

*Department of Gastroenterology, Chenggong Hospital, Xiamen University, and The 174th Hospital of the PLA, Xiamen, Fujian, China
†Medical Department of Graduate College of Nanchang University, Nanchang, Jiangxi, China

Overexpression of Pokemon, which is an erythroid myeloid ontogenic factor protein, occurs in different cancers, including hepatocellular carcinoma (HCC). Pokemon is also reported to have an oncogenic activity in various human cancers. This study investigated the effect of Pokemon knockdown on the regulation of HCC growth. POK shRNA suppressed the expression of Pokemon protein in HepG2 cells compared to the negative control vector-transfected HCC cells. Pokemon knockdown also reduced HCC cell viability and enhanced cisplatin-induced apoptosis in HCC cells. AKT activation and the expression of various cell cycle-related genes were inhibited following Pokemon knockdown. These data demonstrate that Pokemon may play a role in HCC progression, suggesting that inhibition of Pokemon expression using Pokemon shRNA should be further evaluated as a novel target for the control of HCC.

Key words: Pokemon; HepG2 cells; PI3K/Akt

Address correspondence to Yichen Dai, Department of Gastroenterology, The 174th Hospital of the PLA, Wenyuan Road, Xiamen, Fujian 361003, China. Tel: +86-592-6335542; Fax: +86-592-6335702; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it