Oncology Research 20(11) Abstracts

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Oncology Research, Vol. 20, pp. 491–498, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13657689382699
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Downregulation of LIMK1 Level Inhibits Migration of Lung Cancer Cells and Enhances Sensitivity to Chemotherapy Drugs

Qingyong Chen,*1 Demin Jiao,*1 Huizhen Hu,* Jia Song,* Jie Yan,* Lijun Wu,* and Li-Qun Xu†

*Department of Respiratory Disease, The 117th Hospital of PLA, Hang Zhou, Zhejiang, P.R. China
†Department of Oncology Disease, The 117th Hospital of PLA, Hang Zhou, Zhejiang, P.R. China

LIM kinase 1 (LIMK1) is a member of a novel class of serine–threonine protein kinases, which plays an important role in malignant transformation. High expression of LIM kinase 1 (LIMK1) has been detected in various invasive cancers. Here, we showed that LIMK1 was overexpressed in non-small cell lung cancer tissues (NSCLC) and cell lines. Expression of LIMK1 was detected in 115 of 150 lung cancer tissues, the frequency being more significant than in lung tissues. In addition, overexpression of LIMK1 was also associated with high TNM stage and lymph node metastasis in NSCLC patients. Moreover, RNAi-mediated suppression of LIMK1 expression markedly inhibited migration and invasion of 801D lung cancer cells. Furthermore, silencing of LIMK1 sensitized 801D cells to chemotherapeutic drugs of cisplatin and gemcitabine. These results indicate that the overexpression of LIMK1 is tightly associated with an aggressive phenotype of lung cancer cells, knockdown of LIMK1 suppressed cell migration and invasion, enhanced chemosensitivity, suggesting a potential therapeutic target for lung cancer.

Key words: LIM kinase 1 (LIMK1); Lung cancer; Migration; Cisplatin; Gemcitabine

1These authors provided equal contribution to this work.
Address correspondence to Dr. Qingyong Chen, Department of Respiratory Disease, The 117th Hospital of PLA, 14 Linyin Road, 310013, Hang Zhou, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Dr. Li-Qun Xu, Department of Oncology Disease, The 117th Hospital of PLA, Hang Zhou 310013, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 499–507, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13685487925095
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Anticancer Effects of Cinnamic Acid in Lung Adenocarcinoma Cell Line H1299-Derived Stem-Like Cells

Yanyan Huang,*1 Fang Zeng,*1 Liyun Xu,* Jihang Zhou,* Xiaoguang Liu,* and Hanbo Le†

*Joint Laboratory of Immunogenomics, Zhoushan Hospital-BIG/CAS, Zhoushan, Zhejiang, People’s Republic of China
†Department of Cardio-Thoracic Surgery, Zhoushan Hospital of Zhejiang Province, Zhoushan, Zhejiang, People’s Republic of China

Lung cancer is a lethal solid tumor with poor prognosis because of its high metastasis and resistance to current therapies. Recently, cancer stem cells (CSCs) were suggested to be major contributors to tumorigenicity and cancer relapse. However, therapeutic targets for lung cancer-related CSCs remain undetermined. The objective of the current study was to investigate whether cinnamic acid (CINN) exerts an antitumor activity against sphere-derived lung CSCs. In this study, CSCs were isolated from the non-small cell lung cancer cell line H1299 as tumor spheres under CSC-selective conditions, and found to have increased tumorigenicity, chemoresistance, and higher expression of both embryonic stem cell-related and drug resistance-related genes compared with parental cells. These observations are consistent with the notion that CSCs are tumorigenic, display the ability to self-renew, and generate differentiated progeny that constitute the majority of cells in tumors. Treatment of sphere-derived stem cells with CINN could diminish their CSC-like abilities by decreasing their proliferation and invasive abilities and facilitating their differentiation into CD133-negative cells. Furthermore, CINN treatment increased the sensitivity of CSCs to chemotherapeutic drugs through apoptosis. Of note, xenotransplantation experiments revealed that CINN combined with cisplatin had a synergistic effect in inhibiting the tumorigenicity of CSCs. In summary, our study clearly revealed the presence of a population of sphere-forming cells with stem-like properties among H1299 cells and CINN can attenuate CSC properties of this stem-like cell population. The potential of CINN should be verified further in future studies of anti-CSC therapy.

Key words: Lung cancer; Cinnamic acid (CINN); Cancer stem cells (CSCs); CD133; Cisplatin

1These authors provided equal contribution to this work.
Address correspondence to Hanbo Le, Department of Cardio-Thoracic Surgery, Zhoushan Hospital of Zhejiang Province, Zhoushan 316004, Zhejiang, China. Tel: +86-0580-2292865; Fax: +86-580-2292518; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Xiaoguang Liu, Joint Laboratory of Immunogenomics, Zhoushan Hospital-BIG/CAS, Zhoushan 316004, Zhejiang, China. Tel: +86-0580-2292869; Fax: +86-580-2292518; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 509–516, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13728687793317
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Mechanical Strain and Growth Factors Regulate Expression of Tenascin-C by OS Cells Additively

Yucai Wang,*1 Yan Han,†1 Yong Ding,* Baoan Ma,* Xiuchun Qiu,* Qingyu Fan,* and Lianhe Zheng*

*Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province, China
†Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province, China

Osteosarcoma (OS) is a kind of malignancy wherein the tumor cells form malignant bone-like or bone tissue. Tenascin-C (TN-C), an important extracellular matrix (ECM) protein, plays an indispensable role in tumor development. However, its regulatory factors, expression, and function in OS pathological process have not been studied extensively. Expression of TN-C is induced by growth factors as well as mechanical strain in fibroblast. So we asked whether mechanical stain and growth factors could induce TN-C expression in OS as well as which pathways were involved in those processes. We found that when mechanical strain was applied to OS cells cultured on silicone membrane, TN-C mRNA and protein levels were increased 10-fold within 8 h compared to the resting control. Likewise, when epidermal growth factors (EGFs) and insulin-like growth factor (IGF-1) were added to cells, TN-C mRNA levels increased sixfold and eightfold, respectively, within 24 h compared to the control. Growth factors (EGF and IGF-1) and mechanical strain had additive effects on the induction of TN-C mRNA expression in OS. Both ROCK-I/II inhibitor and MEK-1 inhibitor inhibited TN-C induction by EGF or IGF-1, while only ROCK-I/II inhibitor had a strong subdued effect on TN-C induction by mechanical strain. Taken together, our findings suggest that growth factors and mechanical strain can induce TN-C in OS through different pathways additively.

Key words: Osteosarcoma (OS); Tenascin-C (TIN-C); Cyclic strain; Epidermal growth factor (EGF); Insulin-like growth factor (IGF-1)

1These authors provided equal contribution to this work.
Address correspondence to Lianhe Zheng, Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, Shaanxi Province, China. Fax: +86-029-84778358; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 517–528, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13747716581336
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Two-Stage Model of Chemically Induced Hepatocellular Carcinoma in Mouse

Min Luo,* Fan Yang,* Sheng-xin Huang,† Zhi-peng Kuang,* Xiao-ling Luo,* Yuan-dong Li,* Ji-ning Wu,* and Yu-an Xie*

*Biomedical Research Center, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China
†Department of Surgery, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, People’s Republic of China

The aim of this study was to develop an efficient and reproducible mouse model for hepatocellular carcinoma (HCC) research and assess the expression of two proto-oncogenes (c-myc and N-ras) and tumor suppressor gene p53 in the carcinogenic process. In this study, we found that diethylnitrosamine initiation with CCl4 and ethanol promotion could induce a short-term, two-stage liver carcinogenesis model in male BALB/c mice, the process of hepatocarcinogenesis including liver damage, liver necrosis/cell death, liver inflammation, liver proliferation, liver hyperplasia, liver steatosis, and liver cirrhosis and hepatocellular nodules, which mimicked the usual sequence of events observed in human HCC. We also identified that the increase in expression of the p53 gene is related to the proliferation of hepatocytes, whereas overexpression of the c-myc and N-ras genes is associated with hepatocarcinogenesis. This animal model may serve as a basis for recapitulating the molecular pathogenesis of HCC seen in humans.

Key words: Hepatocellular carcinoma (HCC); Mouse model; Diethylnitrosamine (DEN); Carbon tetrachloride (CCl4); Ethanol

Address correspondence to Yu-an Xie, Ph.D., Biomedical Research Center, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China. Tel: +86-771-2811565; Fax: +86-771-5312000; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 529–536, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13747716581372
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Characterization of Ovarian Cancer Cell Metabolism and Response to Chemotherapy by 31P Magnetic Resonance Spectroscopy

Yoram Abramov,*1 Shani Carmi,†1 Shaoul O. Anteby,‡ and Israel Ringel†

*Department of Obstetrics and Gynecology, Carmel Medical Center, Rappaport Faculty of Medicine, Technion University, Haifa, Israel
†Department of Pharmacology, Hadassah Hebrew University Medical School, Jerusalem, Israel
‡Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical School, Jerusalem, Israel

We aimed to characterize the 31P magnetic resonance spectra of various ovarian cancer cell lines exhibiting differences in cytotoxic drug resistance. We examined the metabolic profile of three different ovarian cancer cell lines, OC238, A2780, and A2780-cisplatin resistant (A2780cisR), including their response to various cytotoxic drugs (paclitaxel, cisplatin, and carboplatin) by 31P magnetic resonance spectroscopy (MRS) in vitro. In the OC238 cell line, there were higher levels of phosphorylcholine, phosphodiesters, and uridine diphosphosugar (UDPS) + nicotinamide adenine dinucleotide phosphate (NADP). In A2780 and A2780cisR cell lines, phosphocreatine gave a high signal, which was absent in the OC238 cell line. In the OC238 cell line, a significant decrease in the glycerophosphoethanolamine, glycerophosphocholine, NADP, and UDPS signals was detected following cytotoxic drug treatment, mainly in response to paclitaxel. A significant increase in the glycerophosphocholine signal was detected following exposure to paclitaxel in both A2780 and A2780cisR cell lines. NADP and UDPS signals increased in response to all drugs in the A2780 cell line; however, in the cisplatin-resistant cell line A2780cisR, no significant change in those signals was detected following cisplatin treatment. We conclude that different ovarian cancer cell lines show characteristic 31P MRS fingerprints and specific metabolic changes in response to cytotoxic drug treatment.

Key words: Ovarian cancer; Paclitaxel; Phospholipid metabolites; Antimitotic drugs; Glycerophosphocholine; Magnetic resonance spectroscopy (MRS)

1These authors provided equal contribution to this work.
Address correspondence to Yoram Abramov, M.D., Department of Obstetrics and Gynecology, Carmel Medical Center, Haifa, Israel. Tel: +972-50-6265495; Fax: +972-4-8343968; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 20, pp. 537–544, 2013
0965-0407/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504013X13775486749335
E-ISSN 1555-3906
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Enhancement of Proliferation and Invasion by MicroRNA-590-5p via Targeting PBRM1 in Clear Cell Renal Carcinoma Cells

Xiangcheng Xiao, Cene Tang, Shan Xiao, Chunyan Fu, and Pingping Yu

Xiangya Hospital, Central-South University, Changsha, China

MicroRNAs (miRNAs) play an important role in cancer development. In our study, miR-590-5p is found to be upregulated in the examined renal cell carcinoma (RCC) cell lines. PBRM1 acts as tumor suppressor in RCC, and its downregulation is associated with increased proliferation and aggressive behavior in RCC. We confirmed that PBRM1 was a direct target of miR-590-5p. miR-590-5p could regulate PBRM1 mRNA and protein expressions in clear cell renal carcinoma (ccRCC) ACHN and 786-O cells. Downregulation of miR-590-5p, which resulted in increased PBRM1, inhibited proliferation and invasion of ccRCC cells. Upregulation of miR-590-5p, which resulted in decreased PBRM1, promoted proliferation and invasion of ccRCC cells. The process of miR-590-5p promoting proliferation was found to be implicated in its inhibition of G1/S transition of ccRCC cells, and the action mechanisms were involved in its downregulation of PBRM1/p21WAF1/CIP1 expression. In conclusion, we identified the role of miR-590-5p, serving as an oncomir in ccRCC, and our findings provide a potential target for the treatment of ccRCC.

Key words: Renal carcinoma; MicroRNA-590-5p; PBRM1; Proliferation; Invasion

Address correspondence to Pingping Yu, Xiangya Hospital, Central-South University, Changsha 410008, China. Tel/Fax: +86-731-13574164457; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it