Oncology Research 21(1) Abstracts

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Oncology Research, Vol. 21, pp. 1–13, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13786659070190
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Induction of Apoptosis by 4-(3-(tert-butylamino)imidazo[1,2-α]pyridine-2-yl) Benzoic Acid in Breast Cancer Cells via Upregulation of PTEN

Sumit Siddharth,*† Purusottam Mohapatra,* Ranjan Preet,* Dipon Das,* Shakti Ranjan Satapathy,* Tathagata Choudhuri,† and Chanakya Nath Kundu*

*Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Bhubaneswar, Odisha, India
†Department of Infection Biology, Institute of Life Sciences, Bhubaneswar, Odisha, India

We have previously reported that 4-(3-(tert-butylamino)imidazo[1,2-α]pyridine-2-yl)benzoic acid, a bicyclic N-fused aminoimidazoles derivative (BNFA-D), possesses anticancer potentiality against breast and kidney cancer cells with minimal toxicities to corresponding normal cells. Here, we explored the mechanism of action of BNFA-D in breast cancer cells using multiple cell-based assays such as MTT, DAPI, FACS, Western blot, and immunoprecipitation. BNFA-D caused apoptosis by upregulating PTEN leading to inhibition of Wnt/TCF signaling cascade and arresting S phase in breast cancer cells. Expression levels of β-catenin, cyclin D1, C-MYC, and phospho-AKT (Ser473) decreased with simultaneous increase in the levels of GSK3β, CK1, and PTEN in BNFA-D-treated MCF-7 cells. Interestingly, silencing of PTEN in breast cancer cells reversed the phenomenon of Wnt/TCF signaling cascade inhibition after BNFA-D treatment.

Key words: Bicyclic N-fused aminoimidazoles derivative (BNFA-D); PTEN; Wnt/TCF signaling; Breast cancer; GSK3β

Address correspondence to Chanakya Nath Kundu, Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Odisha, 751024, India. Tel : +91-0674-272-5466; Fax: +91-0674-272-5732; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 15–21, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13786659070235
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Anti-inflammatory Effect of Full-Length Adiponectin and Proinflammatory Effect of Globular Adiponectin in Esophageal Adenocarcinoma Cells

Rong Zhang,*† Jie Wu,* Dong Liu,* Hu Shan,† and Jun Zhang*

*Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
†Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education, Xi’an, Shaanxi Province, China

Adiponectin, an adipocyte-derived hormone with anti-inflammatory and antitumor activity, inhibits esophageal adenocarcinoma (EAC) cell proliferation and induces apoptosis. Chronic inflammation is a key process involved in initiation and progression of EAC, but the roles and mechanisms of adiponectin in inflammation have not been fully understood in EAC. We aimed to analyze the effects of two types of adiponectin, full-length adiponectin (f-Ad) and globular adiponectin (g-Ad), on inflammatory factors’ expression and explore the roles of ROS/NF-κB signaling pathway in adiponectin-regulated inflammation in EAC cells. It was found that f-Ad and g-Ad differently regulated both mRNA and protein levels of TNF-α, IL-8, and IL-6 in a dose-dependent manner in OE19 cells. g-Ad apparently induced TNF-α, IL-8, and IL-6 production, which was inhibited by PDTC or NAC, and increased intracellular ROS levels and NF-κB p65 activation, whereas f-Ad significantly suppressed production of inflammatory factors and NF-κB p65 activation and also decreased the intracellular ROS levels. In conclusion, the study demonstrated that g-Ad exerts a proinflammatory effect whereas f-Ad appears to induce an anti-inflammatory effect in a ROS/NF-κB-dependent manner in OE19 cells.

Key words: Esophageal adenocarcinoma (EAC); Adiponectin; Inflammation; Inflammatory factors

Address correspondence to Jun Zhang, No. 157, Xi Wu Road, Xi’an 710004, Shaanxi Province, China. Tel/Fax: +86 29 87678009; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 23–31, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13786659070271
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Restoration of INK4a/ARF Gene Inhibits Cell Growth and Cooperates With Imatinib Mesylate in Philadelphia Chromosome-Positive Leukemias

Yuansong Bai,* Zhenxia Lu,* Yumei Lin,* Butong Sun,* Shibao Wang,* and Guanjun Wang†

*Department of Hematology/Oncology, China–Japan Union Hospital of Jilin University, Changchun, Jilin, China
†Department of Hematology/Oncology, The First Hospital of Jilin University, Changchun, Jilin, China

VSV-G-pseudotyped lentiviral vectors expressing p16INK4a or p14ARF were used to infect at high-efficiency Philadelphia chromosome (Ph)-positive leukemia cell lines lacking endogenous transcripts. Restoration of p16INK4a accumulated cells in the G0/G1 phase of cell cycle and restoration of p14ARF induced their apoptosis, followed by significant growth inhibition. Transduction of primary blast cells from chronic myeloid leukemia in blast crisis (CML-BC) and Ph-positive acute lymphoblastic leukemia (ALL) with p16INK4a or p14ARF virus also resulted in cell growth inhibition and/or apoptosis with a patient-to-patient variation, whereas clonal growth and differentiation of cord blood progenitor cells were not affected by enforced expression of INK4a/ARF. Furthermore, upon viral transduction at low multiplicity of infection, INK4a/ARF potentiated the effect of imatinib mesylate on Ph-positive leukemia cell lines in an additive but not synergistic manner. These results suggest that INK4a/ARF protein-mimetic agents may be promising options for Ph-positive leukemias in combination with imatinib mesylate.

Key words: INK4a/ARF; Imatinib; Philadelphia chromosome (PH)-positive leukemia; Lentiviral vector

Address correspondence to Guanjun Wang, M.D., Department of Hematology/Oncology, The First Hospital of Jilin University, Changchun, Jilin 130021, China. Tel: +86-431-88782352; Fax: +86-431-85654528; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 33–41, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13786659070316
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Overexpression of Bmi-1 Induces the Malignant Transformation of Gastric Epithelial Cells In Vitro

Yinting Chen,*1 Guoda Lian,*1 Qiubo Zhang,* Linjuan Zeng,† Chenchen Qian,* Shaojie Chen,* and Kaihong Huang*

*Department of Gastroenterology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China
†Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China

Oncogene Bmi-1 (B-cell-specific Moloney murine leukemia virus integration site 1) has attracted much attention for its involvement in the initiation of a variety of tumors. Our previous study showed that Bmi-1 was highly expressed in gastric cancer and correlated with patient prognosis. However, whether aberrant Bmi-1 expression was critical for the transformation of gastric epithelial cells remains unknown. In this study, we stably expressed Bmi-1 in a human gastric epithelial immortalized cell line, GES-1. The overexpression of Bmi-1 promoted cell growth and proliferation, inhibited apoptosis, enhanced clone formation capability, possessed the characteristics of anchorage-independent growth, and increased migration and invasion abilities. Therefore, our findings demonstrated that ectopic expression of Bmi-1 played an important role in the malignant transformation of gastric epithelial cells.

Key words: B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1); Malignant transformation; Gastric epithelial cells; Gastric cancer

1These authors provided equal contribution to this work.
Address correspondence to Kaihong Huang, Department of Gastroenterology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou 510120, China. Tel: +86-20-8133-2489; Fax: +86-20-8133-2244; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 43–50, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13793555706722
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Inhibition of Cell Proliferation and Increase of Chemosensitivity by Simultaneous Knockdown of XIAP and Survivin in Pancreatic Carcinoma Cells

Jianyi Yang,* Jianhui Ouyang,† Linqi Ouyang,‡ Lu Ouyang,* Yuxiang Chen*

*Department of Pancreatic Biliary Surgery, Xiangya Hospital, Central South University, Changsha, China
†Medical Center, Third Xiangya Hospital, Central South University, Changsha, China
‡Department of Pharmacy, First Affiliated Hospital, Hunan University of Traditional Chinese Medicine, Changsha, China

At present, classic therapies provide limited benefits to the survival of patients with pancreatic cancer. However, clinically available gene therapy strategies have not been well established. This study investigates the effect of shRNA-mediated inhibition of XIAP and survivin expression on the proliferation, apoptosis, and chemosensitivity of pancreatic cancer cells. Stable inhibition of XIAP and survivin expression in SW1990 and Panc-1 pancreatic cancer cells was established by lentivirus-carried shRNAs. The mRNA and protein expression of XIAP and survivin were detected by real-time PCR and Western blot, respectively. Cell proliferation was measured by MTT assay, and apoptosis was detected by caspase-3/7 activity and Hoechst33342 staining. The lentivirus-carried shRNA significantly inhibited XIAP and survivin expression. Simultaneous inhibition of XIAP and survivin expression in pancreatic cells significantly reduced cell proliferation, increased caspase-3/7 activity, and increased cell sensitization to 5-FU and gemcitabine treatments compared to inhibition of XIAP or surviving expression alone. However, simultaneous silencing of XIAP and survivin showed no significant difference in inducing cell apoptosis compared to silencing of XIAP or survivin expression alone. Simultaneous inhibition of XIAP and survivin expression may be an effective strategy for gene therapy of pancreatic cancer.

Key words: Pancreatic cancer; RNA interference (RNAi); X-linked apoptosis inhibiting protein (XIAP); Survivin; Lentivirus; Proliferation; Apoptosis; Chemosensitivity

Address correspondence to Yuxiang Chen, M.D., Ph.D., 87 Xiangya Road, Changsha, Hunan 410008, China. Tel: +86 731 84327971; Fax: +86 731 84327987; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 51–57, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13793555706768
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

In Vitro Characterization of Stem Cell-Like Properties of Drug-Resistant Colon Cancer Subline

Dong Yang,*†1 Haijuan Wang,*1 Jinlong Zhang,† Chunxiao Li,* Zhong Lu,† Jin Liu,† Chen Lin,* Guixin Li,† and Haili Qian†

*State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
†Department of Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China

The objective of this study was to investigate the stem cell-like properties of drug-resistant colon cancer cells. Oxaliplatin was used to induce the drug-resistant subline of HCT116p53+/+ cell line. The stem cell-like characteristics of the drug-resistant subline were assayed for the proliferation capacity, cell cycle, adhesion, invasion, multiple drug resistance, and clone sphere formation capacity. The expression of ABCG2 (ATP-binding cassette superfamily G member 2) and “stemness” indicators SOX2 (SRY-related HMG box-containing transcription factor-2) and OCT4 (octamer-binding transcription factor 4) was determined by Western blot. We established the HCT116p53+/+-oxaliplatin subline (HCT116p53+/+OXA), which was resistant to oxaliplatin with a resistance index (RI) of 3.03 ± 0.14. The HCT116p53+/++OXA was also resistant to Taxol, showing lower proliferation, higher adhesion and invasion ability, greater proportion of G0/G1 phase, and higher sphere-forming capacity than its parental cells. SOX2, OCT4, and ABCG2 were expressed at higher levels in drug-resistant cells than in their parental cells. We verified that the HCT116p53+/+OXA was enriched with cancer stem cell properties and provided an ideal cell model for drug-resistance study.

Key words: Drug-resistant cells; Oxaliplatin; ATP-binding cassette superfamily G member 2 (ABCG2); SRY-related HMG box-containing transcription factor-2 (SOX2); Octamer-binding transcription factor 4 (OCT4)

1These authors provided equal contribution to this work.
Address correspondence to Guixin Li, Department of Oncology, Affiliated Hospital of Weifang Medical University, #7166 BaoTong West Street, Weifang, Shandong 261000, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Haili Qian, State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 59–65, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13793555706803
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Involvement of Oncogenic Protein β-Catenin in LPS-Induced Cytotoxicity in Mouse Mononuclear Leukemia RAW 264.7 Cells

Naoki Koide, Yoshikazu Naiki, Erdenezaya Odkhuu, Bilegtsaikhan Tsolmongyn, Takayuki Komatsu, Kiyoaki Ito, Tomoaki Yoshida, and Takashi Yokochi

Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

A toll-like receptor 4 (TLR-4) ligand, lipopolysaccharide (LPS) not only activates expression and secretion of inflammatory cytokines, but it also often shows toxicity in monocytes. Whether an oncogenic protein, β-catenin, is positively involved in LPS-induced cytotoxicity in a mouse leukemic monocyte cell line, RAW 264.7, was examined. TWS119, a GSK-3β inhibitor, increased LPS-induced β-catenin accumulation in the nucleus and augmented LPS-induced cytotoxicity. Cardamonin, a β-catenin inhibitor, inhibited LPS-induced β-catenin accumulation in the nucleus and reduced LPS-induced cytotoxicity. To confirm that β-catenin is involved in LPS-induced cytotoxicity, silencing of β-catenin expression by siRNA was carried out. The results were that knockdown of β-catenin reduced LPS-induced cytotoxicity. Interestingly, Cardamonin treatment or β-catenin silencing reduced LPS-induced endoplasmic reticulum (ER) stress responses such as PERK and e1F-2α phosphorylation and CHOP expression. Moreover, TWS119 increased LPS-induced ER stress responses. On the basis of these results, the oncogenic protein β-catenin is considered to be positively involved in LPS-induced cytotoxicity, possibly by downregulating ER stress responses.

Key words: RAW 264.7 cells; LPS cytotoxicity; β-Catenin; Endoplasmic reticulum (ER) stress

Address correspondence to Naoki Koide, Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it