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重组人乳铁蛋白表达腺病毒对宫颈癌的体内外生长抑制作用。

Growth suppression effects of recombinant adenovirus expressing human lactoferrin on cervical cancer in vitro and in vivo.

机构信息

College of Animal Science and Technology, Northwest A&F University, No. 22 Xinong Road, Yangling, PR China.

出版信息

Cancer Biother Radiopharm. 2011 Aug;26(4):477-83. doi: 10.1089/cbr.2010.0937.

Abstract

Human lactoferrin (hLF) is a multifunctional glycoprotein that can inhibit cancer growth. The molecular mechanism of hLF-induced tumor growth inhibition is incompletely understood. Moreover, the adenovirus vector-mediated hLF (Ad-hLF) gene therapy on cervical cancer has not been yet characterized. In this study, the replication-deficient Ad-hLF was used to explore tumor growth suppression effects on cervical cancer in vitro and in vivo. The results showed that the recombinant adenovirus encoding hLF delivery resulted in a more differential tumor growth inhibition, and this growth arrest was caused by cell cycle inhibition at G2/M phase. In addition, Fas, a death-inducing receptor, and Bax, a member of pro-apoptotic Bcl-2 family, were increased in the sample of cervical cancer tissue treated by Ad-hLF. Further, it was also observed that caspase-3 was activated and the expression of anti-apoptotic Bcl-2 was decreased. These results indicated that the growth inhibitory effects of Ad-hLF on cervical cancer were caused by elevated expression of Fas and decreased the ratio of anti- to pro-apoptotic molecule Bcl-2/Bax.

摘要

人乳铁蛋白(hLF)是一种多功能糖蛋白,能够抑制肿瘤生长。hLF 诱导肿瘤生长抑制的分子机制尚不完全清楚。此外,尚未对腺病毒载体介导的 hLF(Ad-hLF)基因治疗宫颈癌进行描述。在本研究中,使用复制缺陷型 Ad-hLF 来体外和体内探索其对宫颈癌的肿瘤生长抑制作用。结果表明,重组腺病毒编码 hLF 传递导致更显著的肿瘤生长抑制,这种生长停滞是由 G2/M 期细胞周期抑制引起的。此外,在 Ad-hLF 处理的宫颈癌组织样本中,死亡诱导受体 Fas 和促凋亡 Bcl-2 家族成员 Bax 的表达增加。此外,还观察到 caspase-3 被激活,抗凋亡 Bcl-2 的表达减少。这些结果表明,Ad-hLF 对宫颈癌的生长抑制作用是由 Fas 的表达增加和抗凋亡分子 Bcl-2/Bax 的比值降低引起的。

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