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Effect of arsenic trioxide on proliferation and
apoptosis of U266 cells and its relationship with the expression variation
of VEGF |
ZHAN Rong, YU Qinghong, HUANG Haobo |
Fujian Institute of Hematology, Department of Hematology, The Affiliated Union Hospital, Fujian Medical University |
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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 ?mol/L. After treatment with 2, 5, 10 ?mol/L As2O3 for 36 hours, dose-dependent apoptosis of U266 cells was observed. After treatment with 2, 5, 10 ?mol/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.
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Issue Date: 05 December 2008
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1 |
Munshi N C, Tricot G, Desikan R, Badros A, Zangari M, Toor A, Morris C, Anaissie E, Barlogie B . Clinicalactivity ofarsenic trioxide for the treatment of multiple myeloma. Leukemia, 2002, 16(9): 1835–1837. doi:10.1038/sj.leu.2402599
|
2 |
Podar K, Anderson K C . The pathophysiologic roleof VEGF in hematologic malignancies: Therapeutic implications. Blood, 2005, 105(4): 1383–1395. doi:10.1182/blood-2004-07-2909
|
3 |
Amadori S, Fenaux P, Ludwig H, O'dwyer M, Sanz M . Use of arsenic trioxide inhaematological malignancies: insight into the clinical developmentof a novel agent. Curr Med Res Opin, 2005, 21(3): 403–411. doi:10.1185/030079904X20349
|
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 multiplemyeloma cells. Blood, 2001, 98(3): 805–813. doi:10.1182/blood.V98.3.805
|
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 thetreatment of multiple myeloma in SCID mice. Eur J Haematol, 2004, 72(3): 166–171. doi:10.1046/j.0902-4441.2003.00194.x
|
6 |
Bellamy W T, Richter L, Frutiger Y, Grogan T M . Expressionof vascular endothelial growth factor and its receptors in hematopoieticmalignancies. Cancer Res, 1999, 59(3): 728–733
|
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 mediatingmultiple myeloma cell growth and migration. Blood, 2001, 98(2): 428–435. doi:10.1182/blood.V98.2.428
|
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 multiplemyeloma cells against apoptosis. Blood, 2004, 104(9): 2886–2892. doi:10.1182/blood-2004-05-1760
|
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 endothelialgrowth factor by human tumors inhibits the functional maturation ofdendritic cells. Nat Med, 1996, 2(10): 1096–1103. doi:10.1038/nm1096-1096
|
10 |
Nakagawa M, Kaneda T, Arakawa T, Morita S, Sato T, Yomada T, Hanada K, Kumegawa M, Hakeda Y . Vascular endothelialgrowth factor (VEGF) directly enhances osteoclastic bone resorptionand survival of mature osteoclasts. FEBSLett, 2000, 473(2): 161–164. doi:10.1016/S0014-5793(00)01520-9
|
11 |
Henriksen K, Karsdal M, Delaisse J M, Engsig M T . RANKL andvascular endothelial growth factor (VEGF) induce osteoclast chemotaxisthrough an ERK1/2-dependent mechanism. J Biol Chem, 2003, 278(49): 48745–48753. doi:10.1074/jbc.M309193200
|
12 |
Hayashi T, Hideshima T, Akiyama M, Raje N, Richardson P, Chauhan D, Anderson K C . Ex vivo induction of multiplemyeloma-specific cytotoxic T lymphocytes. Blood, 2003, 102(4): 1435–1442. doi:10.1182/blood-2002-09-2828
|
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-inhibitorof VEGF receptors, blocks the growth and migration of multiple myelomacells in the bone marrow microenvironment. Blood, 2004, 103(9): 3474–3479. doi:10.1182/blood-2003-10-3527
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