Influence of E3 region on conditionally replicative adenovirus mediated cytotoxicity in hepatocellular carcinoma cells
Influence of E3 region on conditionally replicative adenovirus mediated cytotoxicity in hepatocellular carcinoma cells
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E3区对条件复制腺病毒介导的肝细胞癌细胞毒性的影响
DOI：
10.4161/cbt.8.12.8445
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发表时间：
2009-06
影响因子：
3.6
通讯作者：
Ye Xun
中科院分区：
文献类型：
--
作者：
Lu Qin;Chen Hong-Zhuan;Yu De-Hong;Liu Fang;Fang Chao;Qin Jie;Zhao Yi;Hu Fang;Liang Min;Guo Xiao-Kui;Ye Xun
采用条件复制腺病毒（CRAd）的病毒治疗是治疗肝细胞癌（HCC）的一种新的靶向策略。在本研究中，我们探索了E3区域对CRAd介导的肝癌细胞毒性的潜在影响，该区域编码几种trail抑制蛋白（E3-6.7 k, E3-10.4 k /14.5K和E3-14.7 k）。制备了两个含有E3区（Ad.ΔE1B）或不含E3区（Ad.ΔE1B.ΔE3）的E1B-55 kda缺失的crad。广告。ΔE1B。ΔE3表现出比Ad更高的细胞杀伤能力。在所有HCC细胞（Hep3B、BEL-7404、BEL-7402、HuH7、PLC/PRF/5和HepG2）中均存在ΔE1B，表明Ad.ΔE1B。ΔE3介导的细胞毒性部分归因于缺乏编码trail抑制蛋白的E3区域。在代表性Hep3B细胞中，Ad.ΔE1B。ΔE3导致线粒体膜电位（MMP）下降，ATP水平明显低于Ad.ΔE1B。此外,广告。ΔE1B。ΔE3诱导早期凋亡细胞和晚期凋亡/坏死细胞的数量分别是Ad.ΔE1B感染组的3倍和4倍。对所有内源性表达TRAIL的HCC细胞的细胞毒性和Ad.ΔE1B诱导Hep3B细胞的MMP下降。ΔE3但不是Ad。ΔE1B可以被一种泛caspase抑制剂z-vad-fmk显著抑制，这表明内源性trail介导的凋亡途径可能与Ad.ΔE1B的细胞杀伤能力有关。ΔE3作用于HCC细胞，尽管可能涉及其他未知机制。我们的发现提供了第一个证据，证明没有E3区域的CRAd可能是HCC病毒治疗的明智选择。
Virotherapy employing conditionally replicative adenovirus (CRAd) represents a novel targeted strategy for the hepatocellular carcinoma (HCC) treatment. In this study, we explored the potential influence of E3 region, which encodes several TRAIL-inhibiting proteins (E3-6.7K, E3-10.4K/14.5K and E3-14.7K), on CRAd mediated cytotoxicity to HCC cells. Two E1B-55 kDa-deleted CRAds containing E3 region (Ad.ΔE1B) or no E3 region (Ad.ΔE1B.ΔE3) were fabricated. Ad.ΔE1B.ΔE3 exhibited higher cytocidal potency than Ad.ΔE1B in all tested HCC cells (Hep3B, BEL-7404, BEL-7402, HuH7, PLC/PRF/5 and HepG2), suggesting that Ad.ΔE1B.ΔE3 mediated cytotoxicity was partly attributed to the absence of E3 region encoding TRAIL-inhibiting proteins. In representative Hep3B cells, Ad.ΔE1B.ΔE3 led to more drop of mitochondrial membrane potential (MMP) and much lower ATP level than Ad.ΔE1B. Moreover, Ad.ΔE1B.ΔE3 induced early apoptotic cells and the late apoptotic/ necrotic cells for three and four times more than those infected by Ad.ΔE1B. The cytotoxicity to all TRAIL endogenously expressing HCC cells and MMP drop of Hep3B cells induced by Ad.ΔE1B.ΔE3 but not Ad.ΔE1B could be significantly inhibited by z-vad-fmk, a pan caspase inhibitor, suggesting that the endogenous TRAIL-mediated apoptotic pathway may be implicated in the cytocidal potency of Ad.ΔE1B.ΔE3 on HCC cells although other unknown mechanisms may be also involved. Our findings provided the first evidence that CRAd without E3 region might be a smart choice for the virotherapy of HCC.
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DOI：
10.1038/nrmicro1927
发表时间：
2008-07
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
44.1
作者：
Dong-Hong Zhao;Jian-Jun Hong;Shi-ying Guo;R. Yang;Jun Yuan;C. Wen;Kaiying Zhou;Chaoxing Li
通讯作者：
Dong-Hong Zhao;Jian-Jun Hong;Shi-ying Guo;R. Yang;Jun Yuan;C. Wen;Kaiying Zhou;Chaoxing Li
DOI：
10.1016/s1470-2045(00)00030-9
发表时间：
2000-11
期刊：
The Lancet. Oncology
影响因子：
--
作者：
J. Gómez-Navarro;D. Curiel
通讯作者：
J. Gómez-Navarro;D. Curiel
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
4.4
作者：
Routes, JM;Ryan, S;Cook, JL
通讯作者：
Cook, JL