The Mechanism of Inhibition Effect of Adenovirus-mediated ING4 
on Human Lung Adenocarcinoma Xenografts in Nude Mice

Abstract

Background and objective The inhibitor of growth 4 (ING4) is an important tumor suppressive gene. It has been proven that ING4 could inhibite the proliferation of many tumors. The aim of this study is to investigate the inhibitory effect and anti-cancer mechanism of adenovirus-mediated ING4 gene on SPC-A1 human lung adenocarcinoma in nude mice. Methods A human lung adenocarcinoma xenograft model was established with SPC-A1 cells in nude mice. A total of 15 tumor-bearing nude mice were randomly divided into three groups, namely, PBS, Ad-GFP, and Ad-ING4. The mice in the three groups were intratumorally injected every other day. Their tumor volumes were continually recorded. The treatment tumors were then removed from the mice and weighed. Tumor inhibition rates were calculated. Cell apoptosis was examined by TUNEL method. Caspase-3, COX-2, Fas, and FasL expressions were investigated by immunohistochemistry SP assay. Results Both tumor weight and volume in the Ad-ING4 group were significantly decreased. The tumor inhibition rate of the mice in the Ad-ING4 group (33.17%±5.24%) was statistically different from that of the mice in the Ad-GFP group (1.31%±0.31%; P<0.05). The apoptotic index of the mice in the Ad-ING4 group (69.23%±6.53%) was also significantly different from those in PBS (17.04%±1.10%) and Ad-GFP groups (18.81%±1.93%; P<0.05). Based on immunohistochemistry SP assay, the results showed that Ad-ING4 may not only upregulate the expressions of caspase-3, Fas, and FasL but also downregulate the expression of COX-2. Conclusion ING4 gene elicited a remarkable growth inhibitory effect on human lung adenocarcinoma xenografts in nude mice. The mechanism is possibly related to an increase in tumor cell apoptosis.

Keywords

• Inhibitor of growth 4
• Lung neoplasms
• Xenografts