5-Aza-2’-deoxycytidine
對人類神經膠質瘤細胞中之分化及侵襲性所造
成的影響
5’-Aza-2-deoxycytidine (5’-AzadC) 是一種抗癌藥物 ( 商品名 ) ，現今
已被用來治療骨髓再生不良症候群和急性骨髓性白血病，然而它對於
人類神經膠質瘤抗侵襲性的療效及機轉仍不太清楚。本研究探討在人
類神經膠質瘤細胞中 5’-AzadC 是否調節細胞侵襲性及其可能機轉。
我們發現惡性人類神經膠質瘤細胞會持續的表現 matrix metalloproteni
nases-2 (MMP-2) ，而且 MMP-2 的活性和腫瘤細胞的惡性度有密切的
關係。在低劑量長時間的處理下我們發現 5’-AzadC 會降低 MMP-2 的
表現而不會引起細胞的死亡，在相同的情況下我們發現 5’-AzadC 會
增加在 U87MG 細胞中 glial fibrillary acidic protein (GFAP) 的表現。 G
FAP 的表現和 MMP-2 的表現呈相反的關係， 5’-AzadC 會引起細胞再
分化的現象，接著會降低細胞的侵襲性。利用 in vitro invasion assay
我們證實了分化中的 U87MG cells 有較低的侵襲性。另外我們發現 5
’-AzadC 會增加 TIMP-2 的表現，顯示 5’-AzadC 不只會減少 MMP-2
的表現，而且也會抑制 MMP-2 的活化。綜合以上結果， 5’-AzadC 可
抑制 MMP-2 的活化、並降低其侵襲性；因此 5’-AzadC 可能可以用來
控制神經膠質瘤的侵襲性，並用於人類神經膠質瘤之治療。
Effects of 5-Aza-2’-deoxycytidine on cell differentiation and invasivenes
s of human glioma cells
5-Aza-2’-deoxycytidine (5-AzadC) is an anti-cancer drug, currently used in the tum
or therapy. However, the underneath mechanisms of the anti-invasiveness effect on
human glioma are still unknown. In the present study, we investigated the possibilit
y of whether 5-AzadC can be used to control the invasiveness of human glioma, an
d the mechanisms by which 5-AzadC regulate cell invasiveness in human glioma c
ells. We found that malignant human glioma cells constitutively expressed matrix
metalloproteinase-2 (MMP-2), and the MMP-2 activities were correlated well with
their malignancies. We demonstrated that 5-AzadC suppressed MMP-2 activity in
U87MG astrocytoma cells and other primary astrocytoma cell lines. 5-AzadC decre
ased MMP-2 expression without causing cell death. At the same conditions, we fou
nd that 5-AzadC increased glial fibrillary acidic protein (GFAP) expression in U87
MG cell suggesting that 5-AzadC induces cell redifferentiation, which was associat
ed with decreased cell invasiveness. Using in vitro invasion assay, we demonstrated
that differentiated U87MG cells exhibited lower invasiveness. In addition, we foun
d that 5-AzadC increased TIMP-2 expression, suggesting that 5-AzadC not only red
uced MMP-2 expression but also inhibited MMP-2 activation. Taken together, thes
e findings support a safer strategy targeting glioma invasiveness in context of gliom
a therapy
