Moalic-Juge Sandra, Liagre Bertrand, Duval Raphaël, Corbiere Cecile, Bianchi Arnaud, Bordji Karim, Bosgiraud Claudine, Beneytout Jean-Louis
Laboratoire de Biochimie, UPRES EA 1085, Faculté de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges Cedex, France.
Int J Oncol. 2002 Jun;20(6):1255-62.
Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to produce an anti-proliferative and pro-apoptotic effect on different types of cancer cell lines. Previously, we demonstrated that high dose of NS-398 (100 microM), a selective cyclooxygenase-2 inhibitor, induced a cell cycle slowing or arrest and, in contrast to low dose (10 microM), a marked decrease in apoptosis in human 1547 osteosarcoma cells. In this study, we investigated particularly the effect of 100 microM NS-398 on p53 and p21 expression, caspase activities and nuclear factor-kappaB (NF-kappaB). We found a correlation between p53, p21 mRNA expression and NF-kappaB activation and, we observed an induction of heat shock protein 70 expression with a large decrease in caspase-3 activity after 100 microM NS-398 treatment. Moreover, the inhibition of apoptosis was correlated with an increase in bcl-2/bax ratio. Our new findings confirm the novel anti-apoptotic property of NS-398 at 100 microM, as we previously found, which contrasts to the described NS-398 pro-apoptotic effect on other cancer cell lines.
非甾体抗炎药（NSAIDs）已被证明对不同类型的癌细胞系具有抗增殖和促凋亡作用。此前，我们证明高剂量的NS-398（100微摩尔），一种选择性环氧化酶-2抑制剂，可诱导细胞周期减慢或停滞，并且与低剂量（10微摩尔）相比，可使人类1547骨肉瘤细胞的凋亡显著减少。在本研究中，我们特别研究了100微摩尔NS-398对p53和p21表达、半胱天冬酶活性及核因子-κB（NF-κB）的影响。我们发现p53、p21 mRNA表达与NF-κB激活之间存在相关性，并且我们观察到在100微摩尔NS-398处理后热休克蛋白70表达增加，而半胱天冬酶-3活性大幅下降。此外，凋亡的抑制与bcl-2/bax比值的增加相关。我们的新发现证实了如我们之前所发现的，100微摩尔NS-398具有新的抗凋亡特性，这与NS-398对其他癌细胞系所描述的促凋亡作用形成对比。
