Radiosensitivity by ING4–IL-24 bicistronic adenovirus-mediated gene cotransfer on human breast cancer cells
Radiosensitivity by ING4–IL-24 bicistronic adenovirus-mediated gene cotransfer on human breast cancer cells
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DOI：
10.1038/cgt.2012.82
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发表时间：
2012-11
影响因子：
6.4
通讯作者：
Y. Zhao;Z. Li;W. Sheng;J. Miao;J. Yang
中科院分区：
文献类型：
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作者：
Y. Zhao;Z. Li;W. Sheng;J. Miao;J. Yang
乳腺癌是女性常见的恶性肿瘤，与较低的五年存活率有关。基因放射治疗，即基因治疗与放射治疗相结合，作为一种新的治疗模式得到了广泛的研究，但大多数研究只评估了一个基因。在此，我们将两个抑癌基因ING4(生长抑制因子家族成员4)和白介素24(IL-24)插入同一双顺反子腺病毒载体中，探讨双基因治疗联合放射治疗对乳腺癌细胞的影响。流式细胞仪检测显示，腺病毒介导的ING4和IL-24表达可抑制MDA-MB-231细胞生长，促进细胞凋亡，并诱导细胞周期停滞于G2/M期。此外，动物模型研究表明，ING4/IL-24基因治疗和放射治疗相结合显著抑制细胞增殖和抑制肿瘤生长(P<；0.05)。从机制上讲，促凋亡反应可能涉及Bax和Caspase-3的上调以及Bcl2的下调。因此，本研究表明，ING4和IL-24两种抑癌基因的共同表达可显著提高MDA-MB-231乳腺癌细胞的放射敏感性。
Breast cancer is a common malignancy among women and is associated with poor 5-year survival rates. Gene radiotherapy, that is, gene therapy combined with radiotherapy, has been extensively studied as a new mode of therapy, but most studies have assessed only one gene. Here, we inserted two anti-oncogenes, ING4 (inhibitor of growth family member 4) and interleukin-24 (IL-24), in the same bicistronic adenovirus vector and explored the effect of dual-gene therapy combined with radiotherapy on breast cancer cells. Flow cytometry assays showed that adenovirus-mediated ING4 and IL-24 expression could suppress growth, promote apoptosis and induce G2/M cell-cycle arrest in MDA-MB-231 cells. Moreover, animal model studies demonstrated that the combination of ING4/IL-24 gene therapy and radiotherapy significantly suppressed cell proliferation and inhibited tumor growth (P< 0.05). Mechanistically, the pro-apoptotic response likely involved the upregulation of Bax and Caspase-3 and the downregulation of Bcl-2. Thus, this study indicates that the co-expression of the two anti-oncogenes, ING4 and IL-24, could significantly promote radiotherapy sensitivity in MDA-MB-231 breast cancer cells.