一种常见病毒的治疗能减缓肿瘤的生长

2011-09-28 13:00 · pobee

这类病毒广泛存在于各类肿瘤细胞中,能够提供一种控制肿瘤生长和消减肿瘤体积的可能途径。

瑞典卡罗林斯卡研究所的研究人员首次证明,对常见的巨细胞病毒(CMV)的治疗有可能抑制脑瘤的生长。这类病毒广泛存在于各类肿瘤细胞中,能够提供一种控制肿瘤生长和消减肿瘤体积的可能途径。该治疗方法可作为传统细胞毒素疗法的一种补充。

巨细胞病毒(CMV)图

巨细胞病毒是一种常见的病毒,70-75%的成人体内都存在这种病毒。正常情况下,它处于休眠状态,并不被人注意,但是当体内形成肿瘤时,该病毒似乎能控制肿瘤细胞中的许多机制。脑癌、乳腺癌、结肠癌和前列腺癌是一类CMV发挥关键作用的肿瘤,研究人员首次证实CMV存在于这类肿瘤中,以及对CMV的治疗能减缓肿瘤的生长。

Cecilia Söderberg-Nauclér 教授称,这项研究表明,92%患者的骨髓瘤都存在CMV,在实验中通过抗病毒药物能抑制肿瘤细胞的生长。这一发现开辟了治疗特定肿瘤的新治疗途径。

之前的研究证实,COX-2酶在多种肿瘤类型中具有高表达量,这一现象在正常组织中不会出现,但是在炎症反应和肿瘤形成过程中却发挥关键作用。在肿瘤细胞中COX-2表达受诱导的原因还不清楚,但该现象往往作为肿瘤发生的不好预测。此外,COX-2抑制剂能降低肿瘤发生的风险,临床研究应用该知识去预防肿瘤。反之,CMV能极大地、特定地激发COX-2的合成,因而它可作为肿瘤的生长控制信号。CMV复制受限于COX-2抑制剂,且被抑制后肿瘤细胞生长就会减缓。相关研究发表在《Clinical Investigation》期刊上。

Cecilia Söderberg-Nauclér 教授称在老鼠实验中,肿瘤细胞生长速度分别下降40%左右(单独服用抗病毒药或COX-2抑制剂)和略低于70%(两者共同服用)。

这是一个非常具有前景和令人振奋的结果。CMV感染不能治愈,也不等同于肿瘤,但是该病毒受抑制后能影响肿瘤的生长。因此,这一研究为肿瘤治疗提供新的途径,并可作为一种辅助治疗。(生物探索译 Pobee)

 

生物探索推荐英文摘要

Detection of human cytomegalovirus in medulloblastomas reveals a potential therapeutic target

Medulloblastomas are the most common malignant brain tumors in children. They express high levels of COX-2 and produce PGE2, which stimulates tumor cell proliferation. Human cytomegalovirus (HCMV) is prevalent in the human population and encodes proteins that provide immune evasion strategies and promote oncogenic transformation and oncomodulation. In particular, HCMV induces COX-2 expression; STAT3 phosphorylation; production of PGE2, vascular endothelial growth factor, and IL-6; and tumor formation in vivo. Here, we show that a large proportion of primary medulloblastomas and medulloblastoma cell lines are infected with HCMV and that COX-2 expression, along with PGE2 levels, in tumors is directly modulated by the virus. Our analysis indicated that both HCMV immediate-early proteins and late proteins are expressed in the majority of primary medulloblastomas. Remarkably, all of the human medulloblastoma cell lines that we analyzed contained HCMV DNA and RNA and expressed HCMV proteins at various levels in vitro. When engrafted into immunocompromised mice, human medulloblastoma cells induced expression of HCMV proteins. HCMV and COX-2 expression correlated in primary tumors, cell lines, and medulloblastoma xenografts. The antiviral drug valganciclovir and the specific COX-2 inhibitor celecoxib prevented HCMV replication in vitro and inhibited PGE2 production and reduced medulloblastoma tumor cell growth both in vitro and in vivo. Ganciclovir did not affect the growth of HCMV-negative tumor cell lines. These findings imply an important role for HCMV in medulloblastoma and suggest HCMV as a novel therapeutic target for this tumor.

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