An Evaluation of HER2-Positive Ovarian Carcinoma Xenografts: From a Novel Therapy to a Noninvasive Monitoring Method

Abstract

Purpose:

Overexpression of the HER2/neu (HER2) is linked to an adverse outcome in ovarian cancer. Short-interfering RNA (siRNA) is a HER2 inhibitor, which in combination with chemotherapy improves survival rate. The aim of this study was to evaluate the efficacy of adenovirus mediated HER2-siRNA in combination with cisplatin (Ad-HER2-siRNA+DDP) on treating HER2-positive ovarian cancer xenografts and explore the effectiveness of ¹³¹I-Herceptin immunoSPECT imaging for monitoring the tumor's progression.

Methods:

Mice with ovarian cancer xenografts were treated with different therapy regimens and imaged at 1, 4, 8, 12, 24, 48, 72, and 96 h postinjection with ¹³¹I-Herceptin. Concurrently, the tumor/background (T/B) ratios were calculated. In addition, HER2 protein expression levels were determined by immunohistochemistry (IHC).

Results:

The in vivo therapy experiments revealed that tumor weight and volume of Ad-HER2-siRNA+DDP group was the least of all. The IHC results further confirmed that HER2 protein level was significantly downregulated in this group. The results of SPECT imaging showed that the T/B ratios at each time point in Ad-HER2-siRNA +DDP group was the lowest (p < 0.05).

Conclusions:

The data demonstrate that the growth of xenografts of human ovarian cancer with high expression of HER2 could be inhibited effectively by Ad-HER2-siRNA+DDP. ¹³¹I-Herceptin had potential use for noninvasive imaging of HER2 expression.