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首页> 外文期刊>Human gene therapy >5/35 fiber-modified conditionally replicative adenovirus armed with p53 shows increased tumor-suppressing capacity to breast cancer cells.
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5/35 fiber-modified conditionally replicative adenovirus armed with p53 shows increased tumor-suppressing capacity to breast cancer cells.

机译：带有p53的5/35纤维修饰的条件复制腺病毒显示出对乳腺癌细胞的肿瘤抑制能力增强。

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Conditionally replicative adenoviruses (CRAds) are widely used for cancer biotherapy and show a significant growth-suppressing effect on many types of cancer. However, it was reported that breast cancer was highly resistant to the infection of traditionally used adenovirus of serotype 5 (Ad5)-based CRAds. Although partial substitution of the fiber protein of replication-deficient Ad5 with that of adenovirus of serotype 35 (Ad35) facilitated infection of breast cancer cells by adenoviral vectors, it is still unknown whether this modification can improve CRAds in their tumor-eliminating capacity. We generated a 5/35 fiber-modified CRAd with a p53 cDNA construct and investigated whether this alteration in fiber region can make CRAds suppress the growth of breast cancer more effectively. Our data reinforced the proposal that 5/35-modified fiber conferred higher adenovirus infectivity for breast cancer cells than natural Ad5 fiber. Interestingly, 5/35 fiber-modified CRAd replicated more efficiently in breast cancer cells than Ad5-based CRAd. We also found 5/35 fiber-modified CRAd mediated higher expression of p53 in breast cancer cells. In vitro, 5/35 fiber-modified CRAd eliminated breast cancer cells more efficiently. Growth of xenograft tumors in nude mice was also significantly retarded by 5/35 fiber-modified CRAd. The 5/35 fiber-modified CRAd suppressed the growth of breast cancer cells more effectively than Ad5-based CRAd, both in vitro and in vivo. Thus CRAd with 5/35 hybrid fiber may be a promising vector for breast cancer treatment.
机译：条件复制腺病毒（CRAds）被广泛用于癌症生物治疗，并显示出对许多类型癌症的显着生长抑制作用。然而，据报道，乳腺癌对基于血清型5（Ad5）的CRAds的传统使用的腺病毒的感染具有高度抗性。尽管用血清型35的腺病毒（Ad35）的复制缺陷型Ad5的纤维蛋白部分替代促进了腺病毒载体对乳腺癌细胞的感染，但仍不清楚这种修饰是否可以改善CRAds的肿瘤清除能力。我们生成了具有p53 cDNA构建体的5/35纤维修饰的CRAd，并研究了纤维区域的这种改变是否可以使CRAds更有效地抑制乳腺癌的生长。我们的数据证实了5/35修饰的纤维赋予乳腺癌细胞比天然Ad5纤维更高的腺病毒感染力的提议。有趣的是，与基于Ad5的CRAd相比，5/35纤维修饰的CRAd在乳腺癌细胞中的复制效率更高。我们还发现5/35纤维修饰的CRAd介导了乳腺癌细胞中p53的更高表达。在体外，5/35纤维修饰的CRAd更有效地消除了乳腺癌细胞。 5/35纤维修饰的CRAd也显着抑制了裸鼠体内异种移植肿瘤的生长。 5/35纤维修饰的CRAd在体外和体内均比基于Ad5的CRAd更有效地抑制了乳腺癌细胞的生长。因此，具有5/35杂合纤维的CRAd可能是用于乳腺癌治疗的有前途的载体。

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