首页> 外文期刊>Carcinogenesis >A novel oncolytic adenovirus selectively silences the expression of tumor-associated STAT3 and exhibits potent antitumoral activity.
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A novel oncolytic adenovirus selectively silences the expression of tumor-associated STAT3 and exhibits potent antitumoral activity.

机译:新型溶瘤腺病毒选择性沉默与肿瘤相关的STAT3的表达,并表现出强大的抗肿瘤活性。

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摘要

Tumor cells acquire the ability to proliferate uncontrollably, resist apoptosis, sustain angiogenesis and evade immune surveillance. Signal transducer and activator of transcription (STAT) 3 regulates all of these processes in a surprisingly large number of human cancers. Consequently, the STAT3 protein is emerging as an ideal target for cancer therapy. This paper reports the generation of an oncolytic adenovirus (M4), which selectively blocks STAT3 signaling in tumor cells as a novel therapeutic strategy. M4 selectively replicated in tumor cells and expressed high levels of antisense STAT3 complementary DNA during the late phase of the viral infection in a replication-dependent manner. The viral progeny yield of M4 in tumor cells was much higher than that of the parent adenoviral mutants, Ad5/dE1A. M4 effectively silenced STAT3 and its target genes in tumor cells while sparing normal cells and exhibited potent antitumoral efficacy in vitro and in vivo. Systemic administration of M4 significantly inhibited tumor growth in an orthotopic gastric carcinoma mouse model, eliminated abdominal cavity metastases and prolonged survival time. In summary, M4 has low toxicity and great potential as a therapeutic agent for different types of cancers.
机译:肿瘤细胞具有不受控制地增殖,抵抗凋亡,维持血管生成和逃避免疫监视的能力。信号转导子和转录激活子(STAT)3调节大量令人惊讶的人类癌症中的所有这些过程。因此,STAT3蛋白正在成为癌症治疗的理想靶标。本文报道了溶瘤腺病毒(M4)的产生,该溶瘤腺病毒可选择性地阻断肿瘤细胞中的STAT3信号传导,作为一种新型治疗策略。 M4在病毒感染的晚期阶段以复制依赖性方式在肿瘤细胞中选择性复制并表达高水平的反义STAT3互补DNA。肿瘤细胞中M4的病毒后代产量远高于亲代腺病毒突变体Ad5 / dE1A。 M4有效沉默沉默肿瘤细胞中的STAT3及其靶基因,同时保留正常细胞,并在体外和体内表现出强大的抗肿瘤功效。在原位胃癌小鼠模型中,M4的全身给药显着抑制了肿瘤的生长,消除了腹腔转移并延长了生存时间。总而言之,M4具有低毒性,并且作为治疗各种类型癌症的巨大潜力。

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