Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Cancer Gene Ther. 2013 Jan;20(1):38-45. doi: 10.1038/cgt.2012.82. Epub 2012 Nov 23.
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.
乳腺癌是女性中常见的恶性肿瘤，与 5 年生存率低有关。基因放疗，即基因治疗与放疗相结合，已被广泛研究为一种新的治疗模式，但大多数研究仅评估了一种基因。在这里，我们将两个抑癌基因 ING4（生长抑制因子家族成员 4）和白细胞介素 24（IL-24）插入同一个双顺反子腺病毒载体中，并探讨了双重基因治疗联合放疗对乳腺癌细胞的影响。流式细胞术检测显示，腺病毒介导的 ING4 和 IL-24 表达可抑制 MDA-MB-231 细胞的生长，促进细胞凋亡，并诱导 G2/M 细胞周期停滞。此外，动物模型研究表明，ING4/IL-24 基因治疗联合放疗可显著抑制细胞增殖并抑制肿瘤生长（P<0.05）。在机制上，促凋亡反应可能涉及 Bax 和 Caspase-3 的上调以及 Bcl-2 的下调。因此，本研究表明，两种抑癌基因 ING4 和 IL-24 的共表达可显著提高 MDA-MB-231 乳腺癌细胞对放疗的敏感性。
