目的：恶性肿瘤细胞逃避Anoikis凋亡的特性是其原位侵袭和远处转移的一个重要原因。本文旨在研究应用人干扰素(IFN)α2a诱导骨肉瘤细胞出现Anoikis凋亡，并深入探讨其产生机理及信号传导途径。方法：采用抑制接触培养法建立细胞Anoikis凋亡诱导模型。观测IFN-α2a诱导骨肉瘤细胞MG- 63产生的Anoikis凋亡。TUNEL法形态学检测MG- 63细胞凋亡，流式细胞仪定量检测细胞凋亡程度和细胞表面整联蛋白受体表达。特异性底物切开法检测半胱氨酸天门冬氨酸特异性蛋白酶 (cysteine aspartate-specific proteases, caspase)信号途径。结果：人IFN-α2a可明显诱导骨肉瘤细胞MG- 63产生Anoikis现象，并诱导了MG- 63细胞caspase-8和caspase-3的活性，但IFN对整联蛋白亚单位α4，α5及αv无明显影响，上述整联蛋白封闭抗体对IFNα-2a诱导的MG- 63细胞Anoikis凋亡无明显影响。结论：人干扰素α2a可以在体外通过调节细胞caspase信号途径，诱导骨肉瘤细胞MG- 63产生Anoikis现象，从而抑制骨肉瘤的转移。

Objective:Survived from Anoikis is one important reason for maliganant tumor performing matastasis and local invasion. The present study focused on the mechanism and signal transduction of osteosarcoma anoikis induced by human interferon (IFN) α2a.Methods:Interferon-α2a induced anoikis was detected on a non-attachment culture model. The osteosarcoma anoikis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling (TUNEL) method. Osteosarcoma cells apoptosis and integrin receptors expression were detected by flow cytometry. The cysteine aspartate-specific proteases (caspase) signal transduction was detected by cleavage of synthethic substractes. Results: Human IFN-α2a induced the anoikis apoptosis of osteosarcoma cell MG- 63, with concomitant upregulation of caspase-8 and caspase-3 activity. The expression of integrin receptor α and αv was not influenced evidently.Conclusion: The present results suggested that human IFN-α2a decreased the metastasis of osteosarcoma by inducing the anoikis of osteosarcoma cell MG- 63. Our results also indicated that caspase signal transduction might regulate this anoikis apoptosis in MG- 63.

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