非甾体类抗炎药对荷瘤小鼠的抗肿瘤作用

Inhibitory effects of non-steroidal anti-inflammatory drugs on tumor growth in mice

目的 比较几种非甾体类抗炎药对小鼠荷瘤肝癌的抑制和诱导凋亡作用。方法 昆明小鼠腋下接种鼠H2 2 肝癌细胞 ,给予布洛芬 ,吲哚美辛和尼美舒利每天灌胃 ,2 1d后处死小鼠称瘤重 ,计算抑瘤率 ,并用电镜和Westernblot等方法观察药物对细胞凋亡和环氧化酶 (cyclooxygenase ,COX)表达的影响。结果 三种药对小鼠肿瘤均有抑制作用 ,高剂量尼美舒利作用最明显 ,抑瘤率为 6 1%和 6 2 % ,各治疗组癌细胞均呈现明显凋亡形态改变。与其它组相比 ,尼美舒利明显下调COX 2的表达。结论 尼美舒利抑瘤作用最明显 ,其次为吲哚美辛和布洛芬 ,诱导细胞凋亡可能是非甾体类抗炎药抑制肝癌的机制之一。

Objective To compare the growth-inhibiting and apoptosis-inducing effects of several non-steroidal anti-inflammatory drugs (NSAIDs) on liver cancer in mice. Methods Kunming breed mice were subcutaneously inoculated with mouse hepatoma H22 cells. Beginning from the following day, the mice were orally administered with ibuprofen, indomethacin or nimesulide, respectively, for 21 days. Tumor apoptosis was quantified with electron microscopy. The expression of COX 1 and COX 2 was examined by Western blot. Results The three kinds of NSAIDs, especially nimesulide, could reduce tumor weight. Typical apoptotic morphological changes were seen in all the 3 treated groups. Western blot analysis revealed that nimesulide greatly reduced COX 2 expression but did not change COX 1 expression. Conclusions This study shows a direct in vivo effect of NSAID-derived drugs in a solid murine hepatoma model. Induction of apoptosis might be one of mechanisms of inhibition of mouse hepatoma by NSAIDs.