Glioblastoma is the most common malignant
brain tumor in humans. We explored the molecular mechanisms how the efficacy of
photofrin based
photodynamic therapy (
PDT) was enhanced by miR-99a transfection in human
glioblastoma cells. Our results showed almost similar uptake of
photofrin after 24 h in different
glioblastoma cells, but p53 wild-type cells were more sensitive to radiation and
photofrin doses than p53 mutant cells.
Photofrin based
PDT induced apoptosis, inhibited cell invasion, prevented angiogenic network formation, and promoted DNA fragmentation and laddering in U87MG and U118MG cells harvoring p53 wild-type. Western blotting showed that
photofrin based
PDT was efficient to block the angiogenesis and cell survival pathways. Further,
photofrin based
PDT followed by miR-99a transfection dramatically increased miR-99a expression and also increased apoptosis in
glioblastoma cell cultures and drastically reduced
tumor growth in athymic nude mice, due to down regulation of
fibroblast growth factor receptor 3 (FGFR3) and PI3K/Akt signaling mechanisms leading to inhibition of cell proliferation and induction of molecular mechanisms of apoptosis. Therefore, our results indicated that the anti-
tumor effects of
photofrin based
PDT was strongly augmented by miR-99a overexpression and this novel combination therapeutic strategy could be used for controlling growth of human p53 wild-type
glioblastomas both in vitro and in vivo.