The studies demonstrated that GRN163L induces altered tumor cell adhesion in animal models and that it may have additional benefit in the prevention of metastasis.
Previous studies demonstrated that GRN163L reduces the tumorigenic potential of a human lung cancer cell line (A549-luc) both in vitro and in vivo and that the cells were morphologically and functionally altered in vitro by GRN163L. Further, GRN163L exposure reduces colony formation and other signs of malignant transformation, while cells treated with a mismatched control drug were unaffected.
In an in vivo model of lung cancer metastasis in which tumor cells from an intravenous injection migrate to, attach and grow in lung tissue, multiple doses of GRN163L over a three-week period from the time of animal inoculation with A549-luc tumor cells resulted in significant reduction in tumor progression.
Data in the present publication demonstrate that these effects are due to specific structural elements of GRN163L. In a series of studies, analogues to GRN163L that differed in the lipid moiety component and the thio-phosphoramidate backbone, or lacked a G-triplet within its sequence, did not elicit similar morphological changes or anti-adhesive properties.
This study also demonstrated that administration of a single dose of GRN163L at the time of animal inoculation in the in vivo model of lung cancer metastasis resulted in decreased tumor burden.