Oncology Research 21(3) Abstracts

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Oncology Research, Vol. 21, pp. 121–127, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13832473329953
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Involvement of Ubiquitin-Conjugating Enzyme E2C in Proliferation and Invasion of Prostate Carcinoma Cells

Song Shuliang,* Cui Lei,† Jing Guangwu,‡ and Liu Changjie§

*Shandong University School of Ocean, Weihai, Shandong, China
†The Fourth People’s Hospital, Laishan District, Yantai City, China
‡Chinese Medicine Hospital, Zhouping, Binzhou City, China
§Pharmacy Department of Affiliated Hospital of Medicine College, Weifang, China

Ubiquitin-conjugating enzyme E2C (UBE2C) has been found to participate in the process of several cancers. However, the role of UBE2C in prostate cancer has not been reported. To investigate the function of UBE2C in prostate cancer, several methods were used. UBE2C promoted the proliferation and viability of prostate cancer cells through MTT and colony formation assay and increased the number of invaded or migrated cells in Matrigel or Transwell assay based on its function of inducing EMT. UBE2C also promoted tumor formation in vivo. Our results suggest that UBE2C acts as an oncogene in prostate cancer progression and may be a candidate marker of diagnosis for this disease.

Key words: Ubiquitin-conjugating enzyme E2C (UBE2C); Prostate cancer; Oncogene; Diagnosis; Prostate

Address correspondence to Liu Changjie, Pharmacy Department of Affiliated Hospital of Medicine College, No.2428, Yuhe Road, Weifang, 261031, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 129–136, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13832473329999
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

MicroRNA-200c Inhibits Apoptosis in Pituitary Adenoma Cells by Targeting the PTEN/Akt Signaling Pathway

Chuangxin Liao,* Wenli Chen,* Xiang Fan,* Xiaobing Jiang,* Lubing Qiu,* Chunhua Chen,† Yonghong Zhu,† and Haijun Wang*

*Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
†Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China

MicroRNAs (miRNAs) are important regulators that are involved in the development of different types of tumors. MicroRNA-200c (miR-200c) has been characterized as a tumor suppressor or oncogene in different cancers. However, the role of miR-200c in pituitary tumorigenesis remains unknown. We observed that miR-200c was overexpressed in pituitary adenoma cell lines. We transfected a miR-200c inhibitor into pituitary adenoma cells (MMQ cell line) to inhibit miR-200c expression and found that the percentage of apoptotic MMQ cells increased. Using bioinformatics analyses, we predicted that the tumor suppressor gene PTEN was targeted by miR-200c, and we confirmed the presence of a functional miR-200c binding site in the 3′-UTR of PTEN using luciferase reporter assays. We determined that the inhibition of miR-200c expression can upregulate PTEN expression and decrease the expression of phosphorylated Akt (p-Akt). Furthermore, the siRNA-mediated knockdown of PTEN abrogated the effect of inhibiting miR-200c expression. Taken together, these findings suggest that miR-200c regulates pituitary tumor formation through the PTEN/Akt signaling pathway. Therefore, we propose that the inhibition of miR-200c could have therapeutic potential in pituitary adenoma.

Key words: MicroRNA; Pituitary adenoma; PTEN/Akt signaling pathway; Apoptosis

Address correspondence to Haijun Wang, M.D., Ph.D., Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. Tel/Fax: +86-20-82393181; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 137–144, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13832473330032
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Curcumin Lowers Erlotinib Resistance in Non-Small Cell Lung Carcinoma Cells With Mutated EGF Receptor

Shanqun Li,*1 Zilong Liu,*1 Fen Zhu,* Xiaohong Fan,† Xiaodan Wu,* Heng Zhao,† and Liyan Jiang†

*Department of Respiratory Medicine, Zhongshan Hospital, Shanghai Medical School, Fudan University, Shanghai, China
†Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China

Non-small cell lung cancer (NSCLC) patients with activating mutations in the epidermal growth factor receptor (EGFR) are responsive to erlotinib, an EGFR-tyrosine kinase inhibitor (EGFR-TKI). However, patients with secondary somatic EGFR mutations are resistant to EGFR-TKI treatment. In this study, we investigated the effect of curcumin on the tumor growth of erlotinib-resistant NSCLC cells. Cell proliferation was determined by MTT assay. Apoptosis was examined using TUNEL staining. Protein expression of genes was determined by Western blot. Tumor growth was assessed in a xenograft mouse model. Results showed that erlotinib had a stronger effect on the induction of apoptosis in erlotinib-sensitive PC-9 cells but showed a weaker effect on erlotinib-resistant H1975 and H1650 cells than cisplatin and curcumin. Furthermore, curcumin significantly increased the cytotoxicity of erlotinib to erlotinib-resistant NSCLC cells, enhanced erlotinib-induced apoptosis, downregulated the expressions of EGFR, p-EGFR, and survivin, and inhibited the NF-κB activation in erlotinib-resistant NSCLC cells. The combination of curcumin and erlotinib exhibited the same effects on apoptosis as the combination of curcumin and cisplatin in erlotinib-resistant NSCLC cells. Moreover, the combined treatment of curcumin and erlotinib significantly inhibited tumor growth of erlotinib-resistant NSCLC cells in vivo. Our results indicate that curcumin is a potential adjuvant for NSCLC patients during erlotinib treatment.

Key words: Non-small cell lung cancer (NSCLC); Curcumin; Erlotinib; Survivin; Drug resistance; NF-κB; Cancer therapy

1These authors provided equal contribution to this work.
Address correspondence to Liyan Jiang, M.D., Ph.D., Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, China. Tel: 0086-21-62821990, ext. 3801; Fax: +86 2132260856; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 145–154, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13841340689573
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

MicroRNA-210 Promotes Proliferation and Invasion of Peripheral Nerve Sheath Tumor Cells Targeting EFNA3

Zhengguang Wang,* Bangliang Yin,† Bing Wang,* Zemin Ma,* Weidong Liu,* and Guohua Lv*

*Department of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha, China
†Department of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, China

MicroRNA (miR) plays an important role in tumorigenesis including malignant peripheral nerve sheath tumor (MPNST). miR-210 downregulation is frequently observed in a variety of tumors. In this study, miR-210 was identified as downregulated in MPNST cells, and its potential target ephrin-A3 (EFNA3) was upregulated in them compared with neurofibroma cells using quantitative real-time (qRT)-PCR. Luciferase reporter assay further demonstrates that EFNA3 is a target of miR-210. Then it is confirmed that miR-210 can regulate EFNA3 mRNA and protein expression in MPNST ST88-14 (NF1 wild-type) and sNF96.2 (NF1 mutant type) cell lines. The functions of miR-210 in MPNST cells were investigated, and the results showed that overexpression of miR-210 increased cellular viability, colony formation, S phase percentage, and invasiveness of MPNST cells. Inversely, inhibition of miR-210 expression induced suppression of proliferation and invasion of MPNST cells. These results suggest that miR-210-mediated EFNA3 promotion of proliferation and invasion of MPNST cells plays an important role in MPNST tumorigenesis and progression. miR-210 and EFNA3 may be candidate novel therapeutic targets for MPNST.

Key words: Malignant peripheral nerve sheath tumor (MPNST); MicroRNA (miR-210); Ephrin-A3 (EFNA3); Proliferation; Invasion

Address correspondence to Guohua Lv, Department of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China. Tel: 86-135-1749-8242; Fax: 86-731-84462461; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 155–164, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13854886566598
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

The Sirtuin Inhibitor Tenovin-6 Upregulates Death Receptor 5 and Enhances Cytotoxic Effects of 5-Fluorouracil and Oxaliplatin in Colon Cancer Cells

Takunori Ueno, Shinji Endo, Rie Saito, Mitsuaki Hirose, Sachiko Hirai, Hideo Suzuki, Kenji Yamato, and Ichinosuke Hyodo

Department of Gastroenterology, University of Tsukuba Graduate School, Tsukuba, Ibaraki, Japan

It has been reported that upregulated SIRT1 (NAD+-dependent class III histone deacetylase) deacetylates the p53 protein, represses its function, and allows for tumor cell growth in various cancers. Here we investigated antitumor effects of tenovin-6, a small-molecule inhibitor of SIRT1 and SIRT2, in various colon cancer cell lines. Tenovin-6 induced apoptosis in all five colon cancer cell lines investigated (two cell lines with wild-type p53 and three with mutant p53) regardless of the p53 mutation status. This effect was accompanied by accumulation of death receptor 5 (DR5) in most cell lines. DR5 silencing in HCT116 cells strongly attenuated tenovin-6-induced apoptosis. We investigated the effect of combining tenovin-6 with conventional anticancer agents 5-fluorouracil (5-FU), SN-38 (an active metabolite of irinotecan), and oxaliplatin. Synergistic antitumor effects of tenovin-6 were observed in combination with either 5-FU or oxaliplatin in vitro. The combination of tenovin-6 and oxaliplatin exhibited potent growth inhibition of HCT116 xenograft tumors in vivo. In conclusion, tenovin-6 induced apoptosis in human colon cancer cells through the activation of the DR5 signaling pathway and enhanced the antitumor properties of 5-FU and oxaliplatin. These results may help develop a novel treatment option for colorectal cancer using a SIRT inhibitor.

Key words: Tenovin-6; Colorectal cancer; Sirtuin 1 (SIRT1); Sirtuin 2 (SIRT2); Death receptor 5 (DR5); Cancer therapy

Address correspondence to Shinji Endo, Department of Gastroenterology, University of Tsukuba Graduate School, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. Tel/Fax: +81-29-853-3218; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 21, pp. 165–171, 2014
0965-0407/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13887748696662
E-ISSN 1555-3906
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Leptin Promotes Metastasis by Inducing an Epithelial–Mesenchymal Transition in A549 Lung Cancer Cells

Helin Feng,*1 Qingyi Liu,†1 Ning Zhang,‡ Lihua Zheng,§ Meixiang Sang,¶ Jiangang Feng,* Jinming Zhang,* Xiangyun Wu,# and Baoen Shan¶

*Department of Orthopedics, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
†Department of Thoracic Surgery, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
‡Department of Cardiology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
§Master of Hebei Medical University, Shijiazhuang, China
¶Research Center, Fourth Hospital of Hebei Medical University and Hebei Cancer Institute, Shijiazhuang, China
#Department of Laboratory, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China

Leptin, an adipocyte-derived cytokine associated with obesity, has been reported to participate in carcinogenesis. Epithelial–mesenchymal transition (EMT) is also considered as a key event in tumor metastasis. The aim of this study is to investigate the mechanism of leptin in the promotion of EMT leading to metastasis in A549 lung cancer cells. We investigated the effect of leptin on migration of A549 cells using wound healing and transwell assays. The incidence of EMT in A549 cells was examined by real-time PCR and immunofluorescence staining. The expression of TGF-β in A549 cells was detected by real-time PCR, and blocking of TGF-β in A549 cells was achieved by siRNA techniques. Additional work was performed using 100 patient samples, which included samples from 50 patients diagnosed with lung cancer and an additional 50 patients diagnosed with lung cancer with metastatic bone lesions. Leptin expression was measured using immunohistochemistry techniques. We demonstrated that leptin can effectively enhance the metastasis of human lung cancer A549 cell line using both wound healing and transwell assays. We also found the incidence of EMT in A549 cells after leptin exposure. Furthermore, we detected the expression of TGF-β in A549 cells, which had been reported to play an important role in inducing EMT. We showed that leptin can significantly upregulate TGF-β at both the mRNA and protein levels in A549 cells. Using siRNA to block the expression of TGF-β in A549 cells, we confirmed the role of TGF-β in the promotion of metastasis and induction of EMT. Furthermore, we found that in patient samples leptin was present at higher levels in samples associated with diagnosis of lung cancer bone metastases tissue than lung cancer tissue. Our results indicated that leptin promoted the metastasis of A549 human lung cancer cell lines by inducing EMT in a TGF-β-dependent manner.

Key words: Leptin; Lung cancer; Metastasis; Epithelial–mesenchymal transition (EMT)

1These authors provided equal contribution to this work and should be considered co-first authors.
Address correspondence to Baoen Shan, Research Center, Fourth Hospital of Hebei Medical University and Hebei Cancer Institute, Shijiazhuang, 050011, China. Tel: +86 311 86095283; Fax: +86 311 86992004; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it