Skip to main content
SpringerLink
Log in

Effect of arsenic trioxide on proliferation and apoptosis of U266 cells and its relationship with the expression variation of VEGF

  • Research Article
  • Published:
Frontiers of Medicine in China Aims and scope Submit manuscript

Abstract

The aim of this article is to explore the effect of arsenic trioxide (As2O3) on the proliferation and apoptosis of myeloma cell line U266 and its relationship with the expression variation of vascular endothelial growth factor (VEGF). The viability and apoptosis of U266 cells were observed by methylthiazolyl-tetrazolium (MTT) assay and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL). The effect of As2O3 on the VEGF expression of U266 cells were tested by enzyme linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) analysis. We found that As2O3 could significantly inhibit the growth of U266 cells, and the concentration for 50% growth inhibition (IC50) was 2 μmol/L. After treatment with 2, 5, 10 μmol/L As2O3 for 36 hours, dose-dependent apoptosis of U266 cells was observed. After treatment with 2, 5, 10 μmol/L As2O3 for 72 hours, a dose-dependent reduction of VEGF in the supernatant of U266 cells culture was found. As far as single cells are concerned, nevertheless, the expression of VEGF mRNA did not vary. So we draw the conclusion that As2O3 could induce the apoptosis of U266 cells and inhibit their proliferation, decrease the tumor load, and lead to the reduction of VEGF in the culture supernatant, but not change the expression of VEGF in single U266 cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Munshi N C, Tricot G, Desikan R, Badros A, Zangari M, Toor A, Morris C, Anaissie E, Barlogie B. Clinical activity ofarsenic trioxide for the treatment of multiple myeloma. Leukemia, 2002, 16(9): 1835–1837

    Article  PubMed  CAS  Google Scholar 

  2. Podar K, Anderson K C. The pathophysiologic role of VEGF in hematologic malignancies: Therapeutic implications. Blood, 2005, 105(4): 1383–1395

    Article  PubMed  CAS  Google Scholar 

  3. Amadori S, Fenaux P, Ludwig H, O’dwyer M, Sanz M. Use of arsenic trioxide in haematological malignancies: insight into the clinical development of a novel agent. Curr Med Res Opin, 2005, 21(3): 403–411

    Article  PubMed  CAS  Google Scholar 

  4. Grad J M, Bahlis N J, Reis I, Oshiro M M, Dalton W S, Boise L H. Ascorbic acid enhances arsenic trioxide-induced cytotoxicity in multiple myeloma cells. Blood, 2001, 98(3): 805–813

    Article  PubMed  CAS  Google Scholar 

  5. Rousselot P, Larghero J, Labaume S, Poupon J, Chopin M, Dosquet C, Marolleau J P, Janin A, Brouet J C, Fermand J P. Arsenic trioxide is effective in the treatment of multiple myeloma in SCID mice. Eur J Haematol, 2004, 72(3): 166–171

    Article  PubMed  CAS  Google Scholar 

  6. Bellamy W T, Richter L, Frutiger Y, Grogan T M. Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies. Cancer Res, 1999, 59(3): 728–733

    PubMed  CAS  Google Scholar 

  7. Podar K, Tai Y T, Davies F E, Lentzsch S, Sattler M, Hideshima T, Lin B K, Gupta D, Shima Y, Chauhan D, Mitsiades C, Raje N, Richardson P, Anderson K C. Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration. Blood, 2001, 98(2): 428–435

    Article  PubMed  CAS  Google Scholar 

  8. Le Gouill S, Podar K, Amiot M, Hideshima T, Chauhan D, Ishitsuka K, Kumar S, Raje N, Richardson P G, Harousseau J L, Anderson K C. VEGF induces MCL-1 upregulation and protects multiple myeloma cells against apoptosis. Blood, 2004, 104(9): 2886–2892

    Article  PubMed  Google Scholar 

  9. Gabrilovich D I, Chen H L, Girgis K R, Cunningham H T, Meny G M, Nadaf S, Kavanaugh D, Carbone D P. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med, 1996, 2(10): 1096–1103

    Article  PubMed  CAS  Google Scholar 

  10. Nakagawa M, Kaneda T, Arakawa T, Morita S, Sato T, Yomada T, Hanada K, Kumegawa M, Hakeda Y. Vascular endothelial growth factor (VEGF) directly enhances osteoclastic bone resorption and survival of mature osteoclasts. FEBS Lett, 2000, 473(2): 161–164

    Article  PubMed  CAS  Google Scholar 

  11. Henriksen K, Karsdal M, Delaisse J M, Engsig MT. RANKL and vascular endothelial growth factor (VEGF) induce osteoclast chemotaxis through an ERK1/2-dependent mechanism. J Biol Chem, 2003, 278(49): 48745–48753

    Article  PubMed  CAS  Google Scholar 

  12. Hayashi T, Hideshima T, Akiyama M, Raje N, Richardson P, Chauhan D, Anderson K C. Ex vivo induction of multiple myeloma-specific cytotoxic T lymphocytes. Blood, 2003, 102(4): 1435–1442

    Article  PubMed  CAS  Google Scholar 

  13. Podar K, Catley L P, Tai Y T, Shringarpure R, Carvalho P, Hayashi T, Burger R, Schlossman R L, Richardson P G, Pandite L N, Kumar R, Hideshima T, Chauhan D, Anderson K C. GW654652, the pan-inhibitor of VEGF receptors, blocks the growth and migration of multiple myeloma cells in the bone marrow microenvironment. Blood, 2004, 103(9): 3474–3479

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Fujian Institute of Hematology, Department of Hematology, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, 350001, China

    Rong Zhan, Qinghong Yu & Haobo Huang

Authors
  1. Rong Zhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qinghong Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Haobo Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rong Zhan.

Additional information

__________

Translated from Journal of Fujian Medical University, 2007, 41(6): 491–494 [译自: 福建医科大学学报]

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhan, R., Yu, Q. & Huang, H. Effect of arsenic trioxide on proliferation and apoptosis of U266 cells and its relationship with the expression variation of VEGF. Front. Med. China 2, 356–360 (2008). https://doi.org/10.1007/s11684-008-0068-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11684-008-0068-0

Keywords

Search

Navigation