Adenovirus-mediated co-expression of ING4 and PTEN cooperatively enhances their antitumor activity in human hepatocellular carcinoma cells
Adenovirus-mediated co-expression of ING4 and PTEN cooperatively enhances their antitumor activity in human hepatocellular carcinoma cells
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腺病毒介导的 ING4 和 PTEN 共表达协同增强其在人肝癌细胞中的抗肿瘤活性
DOI：
10.1093/abbs/gmw062
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发表时间：
2016-08-01
影响因子：
3.7
通讯作者：
Wei, Wenxiang
中科院分区：
文献类型：
--
作者：
Rakshit, Nargis;Yang, Sijun;Wei, Wenxiang
生长抑制因子4（inhibitor of growth 4，ING 4）和10号染色体缺失的张力蛋白磷酸酶同源物（phosphatase and tensin homolog deleted on chromosome 10，PTEN）是已知的与肿瘤发生、发展密切相关的肿瘤抑制因子。研究发现ING 4和PTEN在鼻咽癌细胞中具有协同抗肿瘤活性。两种肿瘤抑制剂在抑制肿瘤细胞生长和激活细胞凋亡方面具有协同作用。在这项研究中，我们研究了它们在肝细胞癌（HCC）细胞中的治疗潜力。构建共表达ING 4和PTEN的重组腺病毒（Ad-ING 4-PTEN），并观察其对肝癌细胞SMMC-7721和HepG 2的抗肿瘤作用。Ad-ING 4-PTEN协同抑制肝癌细胞的生长、诱导凋亡、抑制侵袭，并调节SMMC-7721细胞的细胞周期。进一步的研究表明，通过Ad-ING 4-PTEN协同作用，ING 4和PTEN的结合可增强细胞周期相关蛋白（p53、p21和cyclin D1）和凋亡因子（Bad、Bcl-2、Bcl-XL和Bax）表达的改变，从而参与细胞周期的调控和凋亡途径的激活，从而产生协同抗肿瘤作用。这些结果表明，ING 4和PTEN的组合可能为HCC提供有效的治疗策略。
Both inhibitor of growth 4 (ING4) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) are well known as tumor suppressors that are closely related to tumor occurrence and progression. It was reported that ING4 and PTEN showed synergistic antitumor activities in nasopharyngeal carcinoma cells. The two tumor suppressors demonstrated synergistic effect on growth inhibition and apoptosis activation. In this study, we investigated their therapeutic potential in hepatocellular carcinoma (HCC) cells. Recombinant adenoviruses co-expressing ING4 and PTEN (Ad-ING4-PTEN) were constructed, and the antitumor effect on SMMC-7721 and HepG2 HCC cells was evaluated. Ad-ING4-PTEN cooperatively inhibited cell growth, stimulated apoptosis, and suppressed invasion in both HCC cells, and regulated cell cycle in SMMC-7721. Further studies showed that the combination of ING4 and PTEN by Ad-ING4-PTEN cooperatively enhanced the alteration of the expression of cell cycle-related proteins (p53, p21, and cyclin D1) and apoptotic factors (Bad, Bcl-2, Bcl-XL, and Bax), which are involved in the regulation of cell cycle and the activation of apoptotic pathways, leading to the synergistic antitumor effect. These results indicate that the combination of ING4 and PTEN may provide an effective therapeutic strategy for HCC.