کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2514693 | 1118479 | 2009 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Impact of alendronate and VEGF-antisense combined treatment on highly VEGF-expressing A431 cells Impact of alendronate and VEGF-antisense combined treatment on highly VEGF-expressing A431 cells](/preview/png/2514693.png)
Bisphosphonates, and more specially nitrogen-containing bisphosphonates, which are in current use for the treatment of bone diseases, demonstrate proapoptotic, antiproliferative, antiangiogenic and anti-invasive properties on tumor cells. The amino-bisphosphonate alendronate is considered as a potential anticancer drug. In the case of A431 cells, which express high levels of VEGF, it had a two-step effect. At 24 h, the antitumor properties of alendronate were counterbalanced by a survival process, which consisted of an enhancement of VEGF expression (mRNA and protein secretion) and TGFα secretion. It was only at 48 h that alendronate displayed the expected antiproliferative and antiangiogenic properties. The first step, in which the PI3K pathway was engaged, could be prevented by the use of a VEGF-antisense oligonucleotide. The combination of such an antisense with small concentrations of alendronate (∼2 μM), which is of the order of clinically used concentrations, was shown to have an antiangiogenic effect as soon as 12 h.
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Journal: Biochemical Pharmacology - Volume 77, Issue 10, 15 May 2009, Pages 1580–1585