Chang J Y, Xia W, Shao R, Hung M C
Department of Tumor Biology and Breast Cancer Basic Research Program, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.
Oncogene. 1996 Oct 3;13(7):1405-12.
Amplification or overexpression of HER-2/neu in human lung cancer has been correlated with poor prognosis and chemoresistance. We have previously reported that the adenovirus type 5 early region 1A (E1A) gene product can suppress HER-2/neu-mediated transformation phenotypes through inhibition of HER-2/neu expression. To find an efficient way to treat HER-2/neu-overexpressing lung cancer with E1A, a replication-deficient adenovirus containing the E1A gene, Ad.E1A(+), was used to transduce E1A into HER-2/neu-overexpressing and low expressing human lung cancer cell lines. Tumour cell growth in vitro and colony formation in soft agarose were greatly inhibited by Ad.E1A(+) transduction in HER-2/neu-overexpressing lung cancer cell lines. In HER-2/neu low expressing cell lines, E1A could not inhibit cell growth in vitro but could reduce the colony formation ability in soft agarose, indicating different effects of E1A in these two types of cancer cells. To test the therapeutic efficacy of E1A to lung cancer by systemic delivery in vivo, tumor-bearing mice were established by intratracheal injection of lung cancer cells and treated by i.v. tail injections of Ad.E1A(+). As a result, Ad.E1A(+) suppressed HER-2/neu overexpression and inhibited intratracheal lung cancer growth. However, no significant tumor suppression effect of Ad.E1A(+) was observed in mice bearing HER-2/neu low expressing cell line when the same therapeutic procedure was followed. Thus, we conclude that systemic delivery of Ad.E1A(+) can efficiently achieve therapeutic effect in HER-2/neu-overexpressing lung cancer in vivo.
人肺癌中HER-2/neu的扩增或过表达与预后不良和化疗耐药相关。我们之前报道过，5型腺病毒早期区域1A（E1A）基因产物可通过抑制HER-2/neu表达来抑制HER-2/neu介导的转化表型。为了找到一种用E1A治疗HER-2/neu过表达肺癌的有效方法，一种含有E1A基因的复制缺陷型腺病毒Ad.E1A(+)被用于将E1A转导至HER-2/neu过表达和低表达的人肺癌细胞系中。在HER-2/neu过表达的肺癌细胞系中，Ad.E1A(+)转导可显著抑制体外肿瘤细胞生长和软琼脂中的集落形成。在HER-2/neu低表达细胞系中，E1A不能抑制体外细胞生长，但可降低软琼脂中的集落形成能力，表明E1A在这两种癌细胞中的作用不同。为了通过体内全身给药来测试E1A对肺癌的治疗效果，通过气管内注射肺癌细胞建立荷瘤小鼠，并通过尾静脉注射Ad.E1A(+)进行治疗。结果，Ad.E1A(+)抑制了HER-2/neu过表达并抑制了气管内肺癌生长。然而，当采用相同治疗程序时，在荷HER-2/neu低表达细胞系的小鼠中未观察到Ad.E1A(+)显著的肿瘤抑制作用。因此，我们得出结论，Ad.E1A(+)的全身给药可在体内对HER-2/neu过表达的肺癌有效实现治疗效果。
