Oncology Research 22(4) Abstracts

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Oncology Research, Vol. 22, pp. 177–183, 2015
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DOI: http://dx.doi.org/10.3727/096504015X14343704124386
E-ISSN 1555-3906
Copyright ©
2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

Cholangiocarcinoma: Present Status and Molecular Aspects of Diagnosis

Xiao-Fang Liu, Kun Tang, Lu-Lu Sui, and Gang Xu

Department of Hepatobiliary Surgery, Affiliated Yantai Yuhuangding Hospital, Qingdao University Medical College, Yantai, China

Cholangiocarcinomas are neoplasms that involve the epithelial cells of the bile duct, also known as cholangiocytes. This disease is difficult to diagnose early, as most symptoms present late in the disease. In addition, the specific anatomic position can causeperiductal extension and result in a very low radical excision rate and a very poor prognosis. Improved understanding of the features underlying the onset of cholangiocarcinoma and its carcinogenic mechanism may lead to early diagnosis and better prognosis. With the development of molecular biology, much has been learned about oncogenes, tumor-suppressor genes, DNA methylation, microRNAs, and the molecular mechanisms of tumor invasion and metastasis. Based on our research and others, this review article will discuss the current status and prospects of early diagnosis of cholangiocarcinoma.

Key words: Cholangiocarcinoma; Epidemiology; Diagnosis; Oncogene; Tumor-suppressor gene; Methylation; Serum tumor markers; MicroRNAs

Address correspondence to Dr. Xiao-Fang Liu, Department of Hepatobiliary Surgery, Affiliated Yantai Yuhuangding Hospital, Qingdao University Medical College, Yantai 264000, China. Tel: +86-535-6691999; Fax: +86-535-6240341; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 22, pp. 185–191, 2015
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DOI: http://dx.doi.org/10.3727/096504015X14343704124340
E-ISSN 1555-3906
Copyright ©
2015 Cognizant Comm. Corp.
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Doxorubicin Inhibits Proliferation of Osteosarcoma Cells Through Upregulation of the Notch Signaling Pathway

Peng Ji,*1 Ling Yu,*1 Wei-Chun Guo,* Hong-Jun Mei,† Xiao-Ju Wang,‡ Hu Chen,* Shuo Fang,* and Jian Yang*

*Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China
†Wuhan No. 5 Hospital, Wuhan, China
Suizhou Central Hospital, Wuhan, China

Doxorubicin plays a major role in the treatment of osteosarcoma disorders. The Notch signaling pathway exerts various biological functions, including cell proliferation, differentiation, and apoptosis. In the present study, we investigated the effects of different doses of doxorubicin on proliferation and apoptosis of osteosarcoma cells with or without Notch signaling. Results found that cellular viability was downregulated while caspase 3 activity and expression were promoted in osteosarcoma cells following treatment with various doses of doxorubicin for 24, 48, and 72 h, and the effects showed a dose- and time-dependent manner. Furthermore, it was found that various doses of doxorubicin activated the Notch signaling pathway, shown by the elevated expression of Notch target genes NOTCH1, HEY1, HES1, and HES5. It was further proved that, after small interfering RNA (siRNA)-mediated knockdown of Notch, the effects of doxorubicin on the viability and apoptosis of osteosarcoma cells were significantly reduced. It was indicated that doxorubicin treatment reduced the proliferation and promoted the apoptosis of osteosarcoma cells, and this effect was mediated by the Notch signaling pathway.

Key words: Doxorubicin; Notch signaling; Osteosarcoma cell; Proliferation; Apoptosis

1These authors provided equal contribution to this work.
Address correspondence to Wei-Chun Guo, Department of Orthopedics, Renmin Hospital of Wuhan University, No. 238 of Jiefang Road, Wuchang District, Wuhan 430060, China. Tel: +86-27-88041911-82209; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 22, pp. 193–201, 2015
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DOI: http://dx.doi.org/10.3727/096504015X14348950540999
E-ISSN 1555-3906
Copyright ©
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Combined Use of Metformin and Everolimus Is Synergistic in the Treatment of Breast Cancer Cells

Yunshan Wang,*†1 Junmin Wei,‡1 Li Li,§ Cong Fan,‡ and Ying Sun‡

*Department of Human Anatomy and Key Laboratory of Experimental Teratology, Ministry of Education, Shandong University School of Medicine, Jinan, Shandong, China
†International Biotechnology R&D Center, Shandong University School of Ocean, Weihai, Shandong, China
‡Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan, Shandong, China
§Department of Pathology, Shandong University School of Medicine, Jinan, Shandong, China

Everolimus inhibits mammalian target of rapamycin (mTOR) and leads to decreased protein synthesis and decreased cancer cell proliferation in many experimental systems. Adenosine 5′-monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR. Histopathological and biochemical studies of breast cancer show frequent dysregulation of the AMPK and the mTOR pathway. Therefore, we investigated the efficacy of the mTOR inhibitor everolimus and metformin in the treatment of breast cancer cells. This study evaluated the in vitro and in vivo effects of everolimus alone or in combination with metformin on breast cancer cells. MTT assay was used to quantify the inhibitory effect of the drugs on breast cancer cells in vitro. SCID mice injected with HCC1428 cells followed by different treatments were used to assess the in vivo efficacy of different agents. Data showed that the combination ofeverolimus and metformin exerted synergistic inhibitory effects on the growth of breast cancer cells both in culture and in a mouse xenograft model. Further, this combination abrogated S6 and 4EBP1phosphorylation. Collectively, we suggest that the combination of everolimus and metformin may be an effective regimen for treatment of breast cancer, hence warranting further evaluation of the combination in the clinic.

Key words: Metformin; Everolimus; Breast cancer; Adenosine 5′-monophosphate-activated protein kinase (AMPK); Mammalian target of rapamycin (mTOR)

1These authors provided equal contribution to this work.
Address correspondence to Junmin Wei, Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China. Tel: +86 531 82169841; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 22, pp. 203–211, 2015
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DOI: http://dx.doi.org/10.3727/096504015X14386062091352
E-ISSN 1555-3906
Copyright ©
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AEG-1 Promotes Metastasis Through Downstream AKR1C2 and NF1 in Liver Cancer

Cong Li,*1 Xia Wu,†1 Wei Zhang,‡1 Jia Li,‡ Huawei Liu,‡ Ming Hao,‡ Junsong Wang,‡ Honghai Zhang,* Gengxia Yang,* Meijun Hao,* Shoupeng Sheng,* Yu Sun,* Jiang Long,* Xiongbing Hu,§ HanshuoZhang,¶ Caixia Hu,* Li Li,# and Jiasheng Zheng*

*Minimally Intervention Therapy Center of Liver Diseases and Oncology, Beijing You An Hospital, Capital Medical University, Beijing, China
†Department of Infectious Disease, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
‡Department of Orthopaedic Surgery, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
§ViewSolid Biotech, Beijing, China
GenoArray Biotech, Suzhou, China
#Institute of Liver Diseases, Beijing You An Hospital, Capital Medical University, Beijing, China

Liver cancer is one of the most lethal cancers, but our knowledge of the molecular mechanism underlying this process remains insufficient. Through deep sequencing and expression regulation analysis in liver cancer cells, we identified two novel factors, AKR1C2 (positive factor) and NF1 (negative factor), as the AEG-1 downstream players in the process of metastasis in liver cancer. They were experimentally validated to have the capacities of regulating cell migration, cell invasion, cell proliferation, and EMT. Further clinic expression and animal model evidence confirmed their functions. Together, our findings provide a new insight into the pharmaceutical and therapeutic use of AEG-1 and downstream AKR1C2 and NF1.

Key words: Metastasis; AEG-1; AKR1C2; NF1

1These authors provided equal contribution to this work.
Address correspondence to Jiasheng Zheng, 8 Youanmen Outside West Road, Beijing 100069, China. Tel: +86 010 83997338; Fax: +86 010 83997628; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Wei Zhang, 28 Fuxing Road, Beijing 100853, China. Tel: +86 010 66887329; Fax: +86 010 66936619; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it .


Oncology Research, Vol. 22, pp. 213–217, 2015
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DOI: http://dx.doi.org/10.3727/096504015X14386062091398
E-ISSN 1555-3906
Copyright ©
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Piceatannol Enhances the Antitumor Efficacy of Gemcitabine in Human A549 Non-Small Cell Lung Cancer Cells

Bin Xu* and Ze-Zhang Tao†

*Department of Oncology, Wuhan University Renmin Hospital, Wuhan, Hubei, P.R. China
†Department of Otolaryngology-Head and Neck Surgery, Wuhan University Renmin Hospital, Wuhan, Hubei, P.R. China

To enhance the anticancer efficacy of gemcitabine in the treatment of non-small cell lung cancer (NSCLC), the potential synergistic effect of piceatannol on gemcitabine cytotoxicity was investigated in the human NSCLC A459 cell line. The MTT cell viability assay showed that piceatannol significantly enhanced the cytotoxic effects of gemcitabine by lowering the gemcitabine IC
50 value. Flow cytometry analysis revealed that piceatannol exerted its pharmacological effect mainly by increasing the late apoptotic population. Western blot analysis showed that gemcitabine induced the expression of the proapoptotic proteins Bad and Bak, and pretreatment with piceatannol further increased Bak expression, leading to an increased number of cells undergoing late apoptosis. The findings from this study show that piceatannol can enhance the cytotoxic effects of gemcitabine by enhancing expression of the proapoptotic protein Bak, thereby providing the rational basis for a novel combination strategy for the treatment of NSCLC.

Key words: Piceatannol; Gemcitabine; Non-small cell lung cancer (NSCLC); Combination regimen; Apoptosis

Address correspondence to Professor Ze-Zhang Tao, Wuhan University Renmin Hospital, No. 99 Zhang-zhidong Road, Wuhan, Hubei 430060, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it ; This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 22, pp. 219–224, 2015
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DOI: http://dx.doi.org/10.3727/096504015X14386062091442
E-ISSN 1555-3906
Copyright ©
2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

siRNA Suppression of NEDD9 Inhibits Proliferation and Enhances Apoptosis in Renal Cell Carcinoma

Jue Wang,* Wen-juan Yang,† Chao Sun,* Yun Luan,* Guang-hui Cheng,* Kai-lin Li,* and Feng Kong*

*Central Laboratory, The Second Hospital of Shandong University, Jinan, China
†Department of Emergency, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, China

Renal cell carcinoma (RCC) is the most lethal of all genitourinary malignancies. NEDD9/HEF1/Cas-L is a member of the Cas protein family and is known as a biomarker in multiple cancer types. In this study, we demonstrate for the first time that NEDD9 was upregulated in RCC tissue and cell lines. Immunohistochemical analysis and quantitative RT-PCR analysis showed low expression of NEDD9 in normal renal tissues and high expression in RCC tissues. In addition, in vitro experiments show that expression of NEDD9 was upregulated in RCC cell lines. Through MTT assay, we observed that NEDD9 knockdown inhibited cell proliferation. Furthermore, flow cytometry analysis showed that NEDD9 downregulation induced apoptosis. Together, our data suggest that abnormal NEDD9 protein expression may be a marker for RCC, and NEDD9 knockdown suppresses cell growth.

Key words: Renal cell carcinoma (RCC); NEDD9; Proliferation; Apoptosis

Address correspondence to Feng Kong, Central Laboratory, The Second Hospital of Shandong University, No.247 Beiyuan Road, Jinan 250033, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 22, pp. 225–233, 2015
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DOI: http://dx.doi.org/10.3727/096504015X14386062091479
E-ISSN 1555-3906
Copyright ©
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Knockdown of Wip1 Enhances Sensitivity to Radiation in HeLa Cells Through Activation of p38 MAPK

Hong-yong Wang,* Zhong-shan Liu,* Ling Qiu,* Jie Guo,* Yun-feng Li,* Jun Zhang,* Tie-jun Wang,* and Xiao-dong Liu†

*Department of Radiotherapy, 2nd Hospital Affiliated to Jilin University, Jilin University, Changchun, Jilin, China
†Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, China

The objectives of the study were to investigate the functional role and potential mechanism of wild-type p53-induced phosphatase (Wip1) in cervical cancer cell line HeLa cells, along with the effect of knockdown of Wip1 in combination with g-irradiation on the HeLa cells. Expression of Wip1 was silenced or overexpressed. After transfection, cell viability was determined. Moreover, γ-irradiation and SB203580 were performed to explore the effect of colony formation and cell apoptosis. Likewise, protein expression levels of p38, p-p38, p53, and p-p53 were assessed in the presence or not of SB203580 and overexpression of Wip1. Both the mRNA and protein levels of Wip1 were significantly decreased by transfection with Wip1-specific small interfering RNA (siRNA) but were significantly increased by transfection with pcDNA3.1-Wip1. Knockdown of Wip1 significantly decreased cell growth and colony formation ability and increased apoptotic rate. Additionally, better results were obtained by knockdown of Wip1 in combination with g-irradiation. The protein expression levels of p-p38 (p < 0.05), p53 (p < 0.01), and p-p53 (p < 0.05) were all significantly increased by knockdown of Wip1. However, application of SB203580 reversed the effects. Our study confirms the important roles of Wip1 in cervical cancer. Knockdown of Wip1 enhances sensitivity to radiation in HeLa cells by inhibiting cell proliferation and inducing apoptosis through activation of p38 MAPK.

Key words: Cervical cancer; Wild-type p53-induced phosphatase (Wip1); p38 MAPK; γ-Irradiation; SB203580

Address correspondence to Tiejun Wang, Department of Radiotherapy, 2nd Hospital Affiliated to Jilin University, 218 Ziqiang Rd, Nanguan District, Changchun, Jilin 130021, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Xiaodong Liu, Department of Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, 1163 Xinmin Ave, Chaoyang District, Changchun, Jilin 130021, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it