Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
August-2015 Volume 12 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2015 Volume 12 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

VEGF‑C inhibition reverses resistance of bladder cancer cells to cisplatin via upregulating maspin

  • Authors:
    • Haipeng Zhu
    • Feng Yun
    • Xiaoxue Shi
    • Dong Wang
  • View Affiliations / Copyright

    Affiliations: Department of Urinary Surgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
  • Pages: 3163-3169
    |
    Published online on: April 24, 2015
       https://doi.org/10.3892/mmr.2015.3684
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The aim of the current study was to elucidate the association between vascular endothelial growth factor C (VEGF‑C) and resistance of bladder cancer cells to cisplatin and the underlying mechanism involving maspin. A total of 32 bladder cancer tissue samples from patients (18 males and 14 females with an average age of 65.9 years) were collected from the Fifth Affiliated Hospital of Zhengzhou University (Zhengzhou, China). All patients had undergone cisplatin‑based combination chemotherapy. In addition, the BIU87 human bladder cancer cell line was cultured and a cisplatin‑resistant subline (BIU87‑CisR) was established by continuous exposure to cisplatin. The mRNA expression levels of VEGF‑C and maspin in tissue samples, BIU87 cells and BIU87‑CisR cells were analyzed by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Targeted inhibition of VEGF‑C in BIU87‑CisR cells was performed using small interfering (si)RNA technology and the alteration in levels of maspin was confirmed by RT‑qPCR and western blot analysis. siRNA‑treated and ‑untreated BIU87‑CisR cells were divided into the following four groups: Control group (no drug treatment), 3 µM cisplatin treated group, 3 µM cisplatin + siRNA treated group and the siRNA treated group. Cell viability following treatment in each group was evaluated by the cell counting kit 8 assay. The cell cycle and apoptotic rate of BIU87‑CisR cells was analyzed by propidium iodide (PI) staining and Annexin V‑PI double staining with flow cytometry. Furthermore, pcDNA‑maspin transfected BIU78‑CisR cells were used to establish the effect of maspin on the sensitivity to cisplatin. VEGF‑C expression in chemoresistant patients and BIU87‑CisR cells was significantly increased compared with chemosensitive patients and normal BIU87 cells, respectively. By contrast, maspin levels were lower in chemoresistant patients and BIU87‑CisR cells. Subsequent to VEGF‑C inhibition, maspin expression was markedly increased. Cisplatin (3 µM) resulted in moderate proliferation inhibition of BIU87‑CisR cells without siRNA pretreatment; however, significant inhibition was observed in the VEGF‑C siRNA treated group. In addition, the cell cycle arrest and apoptosis induced by cisplatin was enhanced by VEGF‑C inhibition. Overexpression of maspin was able to improve the sensitivity of BIU87‑CisR cells to cisplatin. In conclusion, the resistance of bladder cancer cells to cisplatin may be induced by upregulation of VEGF‑C, and inhibition of VEGF‑C reverses resistance by elevating maspin expression levels.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

View References

1 

Xu W, Wang F, Ying L and Wang HH: Association between glutathione S-transferase M1 null variant and risk of bladder cancer in Chinese Han population. Tumour Biol. 35:773–777. 2014. View Article : Google Scholar

2 

Costantini C and Millard F: Update on chemotherapy in the treatment of urothelial carcinoma. Scientific World Journal. 11:1981–1994. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Shirato A, Kikugawa T, Miura N, Tanji N, Takemori N, Higashiyama S and Yokoyama M: Cisplatin resistance by induction of aldo-keto reductase family 1 member C2 in human bladder cancer cells. Oncol Lett. 7:674–678. 2014.PubMed/NCBI

4 

Galluzzi L, Vitale I, Michels J, Brenner C, Szabadkai G, Harel-Bellan A, Castedo M and Kroemer G: Systems biology of cisplatin resistance: Past, present and future. Cell Death Dis. 5:e12572014. View Article : Google Scholar : PubMed/NCBI

5 

Ding M, Fu X, Tan H, Wang R, Chen Z and Ding S: The effect of vascular endothelial growth factor C expression in tumor-associated macrophages on lymphangiogenesis and lymphatic metastasis in breast cancer. Mol Med Rep. 6:1023–1029. 2012.PubMed/NCBI

6 

Ciobanu M, Eremia IA, Crăiţoiu S, Mărgăritescu CL, Stepan A, Pătraşcu V, Georgescu CC, Cernea D and Dumitrescu D: Lymphatic microvessels density, VEGF-C and VEGFR-3 expression in 25 cases of breast invasive lobular carcinoma. Rom J Morphol Embryol. 54:925–934. 2013.

7 

Liu J, Cheng Y, He M and Yao S: Vascular endothelial growth factor C enhances cervical cancer cell invasiveness via upregulation of galectin-3 protein. Gynecol Endocrinol. 30:461–465. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Ma DM, Xu YP and Zhu L: Expression of vascular endothelial growth factor C correlates with a poor prognosis based on analysis of prognostic factors in patients with cervical carcinomas. J Obstet Gynaecol Res. 37:1519–1524. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Cho HJ, Kim IK, Park SM, et al: VEGF-C mediates RhoGDI2-induced gastric cancer cell metastasis and cisplatin resistance. Int J Cancer. 135:1553–1563. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Snoeren N, Emmink BL, Koerkamp MJ, et al: Maspin is a marker for early recurrence in primary stage III and IV colorectal cancer. Br J Cancer. 109:1636–1647. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Machowska M, Wachowicz K, Sopel M and Rzepecki R: Nuclear location of tumor suppressor protein maspin inhibits proliferation of breast cancer cells without affecting proliferation of normal epithelial cells. BMC Cancer. 14:1422014. View Article : Google Scholar : PubMed/NCBI

12 

Lopez-Ayllon BD, Moncho-Amor V, Abarrategi A, Ibañez de Cáceres I, Castro-Carpeño J, Belda-Iniesta C, Perona R and Sastre L: Cancer stem cells and cisplatin-resistant cells isolated from non-small-lung cancer cell lines constitute related cell populations. Cancer Med. 3:1099–1111. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Zhou BH, Huang JN, Zuo YL, Li BJ, Guo Q, Cui BC, Shao WY, Du J and Bu XZ: 2a, a novel curcumin analog, sensitizes cisplatin-resistant A549 cells to cisplatin by inhibiting thioredoxin reductase concomitant oxidative stress damage. Eur J Pharmacol. 707:130–139. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Ajani JA, Wang X, Song S, et al: ALDH-1 expression levels predict response or resistance to preoperative chemoradiation in resectable esophageal cancer patients. Mol Oncol. 8:142–149. 2014. View Article : Google Scholar :

15 

Shen DW, Pouliot LM, Hall MD and Gottesman MM: Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes. Pharmacol Rev. 64:706–721. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Jayachandran G, Ueda K, Wang B, Roth JA and Ji L: NPRL2 sensitizes human non-small cell lung cancer (NSCLC) cells to cisplatin treatment by regulating key components in the DNA repair pathway. PLoS One. 5:e119942010. View Article : Google Scholar : PubMed/NCBI

17 

Ling KS, Chen GD, Tsai HG, Lee MS, Wang PH and Liu FS: Mechanisms involved in chemoresistance in ovarian cancer. Taiwan J Obstet Gyne. 44:209–217. 2005. View Article : Google Scholar

18 

Patel NP, Pattni BS, Abouzeid AH and Torchilin VP: Nanopreparations to overcome multidrug resistance in cancer. Adv Drug Deliver Rev. 65:1748–1762. 2013. View Article : Google Scholar

19 

Hour TC, Lai YL, Kuan CI, et al: Transcriptional up-regulation of SOD1 by CEBPD: a potential target for cisplatin resistant human urothelial carcinoma cells. Biochem Pharmacol. 80:325–334. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Gutekunst M, Mueller T, Weilbacher A, Dengler MA, Bedke J, Kruck S, Oren M, Aulitzky WE and van der Kuip H: Cisplatin hypersensitivity of testicular germ cell tumors is determined by high constitutive Noxa levels mediated by Oct-4. Cancer Res. 73:1460–1469. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Zhang J, Zhu Z, Sun Z, Sun X, Wang Z and Xu H: Survivin gene expression increases gastric cancer cell lymphatic metastasis by upregulating vascular endothelial growth factor-C expression levels. Mol Med Rep. 9:600–606. 2014.

22 

Li D, Xie K, Ding GT, Li J, Chen K, Li H, Qian J, Jiang C and Fang J: Tumor resistance to anti-VEGF therapy through up-regulation of VEGF-C expression. Cancer Lett. 346:45–52. 2014. View Article : Google Scholar

23 

Hua KT, Lee WJ, Yang SF, Chen CK, Hsiao M, Ku CC, Wei LH, Kuo ML and Chien MH: Vascular endothelial growth factor-C modulates proliferation and chemoresistance in acute myeloid leukemic cells through an endothelin-1-dependent induction of cyclooxygenase-2. Biochim Biophys Acta. 1843:387–397. 2014. View Article : Google Scholar

24 

Stanton MJ, Dutta S, Zhang H, Polavaram NS, Leontovich AA, Hönscheid P, Sinicrope FA, Tindall DJ, Muders MH and Datta K: Autophagy control by the VEGF-C/NRP-2 axis in cancer and its implication for treatment resistance. Cancer Res. 73:160–171. 2013. View Article : Google Scholar :

25 

Zou Z, Anisowicz A, Hendrix MJ, Thor A, Neveu M, Sheng S, Rafidi K, Seftor E and Sager R: Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells. Science. 263:526–529. 1994. View Article : Google Scholar : PubMed/NCBI

26 

Taskiran C, Erdem O, Onan A, Vural C, Arisoy O, Yildiz S and Guner H: Maspin expression in endometrial hyperplasia and carcinoma and its relation with angiogenesis. Eur J Gynaecol Oncol. 35:134–139. 2014.

27 

Berardi R, Morgese F, Onofri A, et al: Role of maspin in cancer. Clin Transl Med. 2:82013. View Article : Google Scholar : PubMed/NCBI

28 

Hirai K, Koizumi K, Haraguchi S, et al: Prognostic significance of the tumor suppressor gene maspin in non-small cell lung cancer. Ann Thorac Surg. 79:248–253. 2005. View Article : Google Scholar

29 

Takanami I, Abiko T and Koizumi S: Expression of maspin in non-small-cell lung cancer: Correlation with clinical features. Clin Lung Cancer. 9:361–366. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Surowiak P, Materna V, Drag-Zalesinska M, Wojnar A, Kaplenko I, Spaczyński M, Dietel M, Zabel M and Lage H: Maspin expression is characteristic for cisplatin-sensitive ovarian cancer cells and for ovarian cancer cases of longer survival rates. Int J Gynecol Pathol. 25:131–139. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhu H, Yun F, Shi X and Wang D: VEGF‑C inhibition reverses resistance of bladder cancer cells to cisplatin via upregulating maspin. Mol Med Rep 12: 3163-3169, 2015.
APA
Zhu, H., Yun, F., Shi, X., & Wang, D. (2015). VEGF‑C inhibition reverses resistance of bladder cancer cells to cisplatin via upregulating maspin. Molecular Medicine Reports, 12, 3163-3169. https://doi.org/10.3892/mmr.2015.3684
MLA
Zhu, H., Yun, F., Shi, X., Wang, D."VEGF‑C inhibition reverses resistance of bladder cancer cells to cisplatin via upregulating maspin". Molecular Medicine Reports 12.2 (2015): 3163-3169.
Chicago
Zhu, H., Yun, F., Shi, X., Wang, D."VEGF‑C inhibition reverses resistance of bladder cancer cells to cisplatin via upregulating maspin". Molecular Medicine Reports 12, no. 2 (2015): 3163-3169. https://doi.org/10.3892/mmr.2015.3684
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu H, Yun F, Shi X and Wang D: VEGF‑C inhibition reverses resistance of bladder cancer cells to cisplatin via upregulating maspin. Mol Med Rep 12: 3163-3169, 2015.
APA
Zhu, H., Yun, F., Shi, X., & Wang, D. (2015). VEGF‑C inhibition reverses resistance of bladder cancer cells to cisplatin via upregulating maspin. Molecular Medicine Reports, 12, 3163-3169. https://doi.org/10.3892/mmr.2015.3684
MLA
Zhu, H., Yun, F., Shi, X., Wang, D."VEGF‑C inhibition reverses resistance of bladder cancer cells to cisplatin via upregulating maspin". Molecular Medicine Reports 12.2 (2015): 3163-3169.
Chicago
Zhu, H., Yun, F., Shi, X., Wang, D."VEGF‑C inhibition reverses resistance of bladder cancer cells to cisplatin via upregulating maspin". Molecular Medicine Reports 12, no. 2 (2015): 3163-3169. https://doi.org/10.3892/mmr.2015.3684
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team