FIG. 6.

Inhibition of KAP overexpression reduces tumorigenicity in nude mice. (A) Antisense (AS) KAP expression inhibited the tumorigenic potential of HeLa cells. Athymic nude mice were injected with 2 × 10⁶ HeLa/KAP-AS1 cells or HeLa/luciferase cells/ml mixed with an equal volume of Matrigel. The cell suspension was injected subcutaneously (bilaterally; 0.5 ml per site) into nude mice. Results are average tumor sizes for six animals in two different sites per experimental condition 3 weeks after injection. The mean tumor size of AS KAP-expressing HeLa cells was significantly less than that of the HeLa-luciferase tumor. Similar relative tumor sizes were obtained from mice injected with HeLa/KAP-AS1 cells and fed with water containing 500 μg of doxycycline/ml (data not shown), compared to sizes of HeLa-luciferase tumors. (B) HeLa/KAP-AS cells showed reduced mitotic index. AS KAP and control tumors harvested after 3 weeks of growth were processed for histological studies (hematoxylin and eosin sections). Top, representative hematoxylin- and eosin-stained section of control (HeLa/Luc) and AS KAP tumors (HeLa/KAP-AS). Mitotic figures are shown as arrows, and apoptotic cells are shown with arrowheads.