Antitumor Effects of Interferon-Alpha on Cell Growth and Metastasis in Human Nasopharyngeal Carcinoma
Antitumor Effects of Interferon-Alpha on Cell Growth and Metastasis in Human Nasopharyngeal Carcinoma
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干扰素-α对人鼻咽癌细胞生长和转移的抗肿瘤作用
DOI：
10.2174/156800912800673293
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发表时间：
2012-06-01
影响因子：
3
通讯作者：
Li, X. -P.
中科院分区：
文献类型：
--
作者：
Liu, X.;Lu, J.;Li, X. -P.
鼻咽癌是一种高度恶性、易转移的肿瘤，发生远处转移时预后很差。最近，免疫疗法正成为一种很有前途的治疗方法。干扰素- α (ifn - α)是临床肿瘤学中使用时间最长的细胞因子。在本研究中，我们检测了ifn - α 1b对鼻咽癌的抗肿瘤作用。结果表明，重组人ifn - α 1b （hifn - α 1b）在体外抑制细胞生长，诱导g1期细胞周期阻滞，增加p16和pRb的表达，降低CCND1和CDK6的表达。体内分析表明，重组腺相关病毒(rAAV)- ifn - α 1b或hifn - α 1b治疗均能抑制肿瘤生长和转移，降低肿瘤内微血管密度，增加细胞凋亡和坏死，延长生存期。值得注意的是，raav - ifn - α 1b或hifn - α 1b治疗导致小鼠血清IL-12和GM-CSF水平显著高于各自的对照组。我们的研究结果表明ifn - α 1b在鼻咽癌中作为一种多功能抗肿瘤药物，可能具有重要的治疗意义。
Nasopharyngeal carcinoma (NPC) is a highly malignant and frequently metastasized tumor, and the prognosis is very poor when distant metastases occur. Recently, immunotherapy is becoming a promising therapeutic approach. Interferon-alpha (IFN-alpha) represents the cytokines exhibiting the longest record of use in clinical oncology. In this study, we examined the antitumor effects of IFN-alpha 1b on NPC. The results showed that recombinant human IFN-alpha 1b (hIFN-alpha 1b) suppressed cell growth, induced a G1-phase cell cycle arrest in vitro, increased the expression of p16 and pRb, and decreased the expression of CCND1 and CDK6. In vivo analyses showed that either recombinant adeno-associated virus (rAAV)-IFN-alpha 1b or hIFN-alpha 1b treatment inhibited tumor growth and metastasis, reduced intratumoral microvessel density, increased cell apoptosis and necrosis, and induced prolonged survival. Notably, rAAV-IFN-alpha 1b or hIFN-alpha 1b treatment led to significantly higher serum levels of IL-12 and GM-CSF in mice compared to respective controls. Our findings suggest that IFN-alpha 1b acts as a multifunctional antitumor agent in NPC, which may have important therapeutic implications.