Several anticancer drugs are ineffective against
brain tumor and do not impact patient survival because they fail to cross the blood-
brain tumor barrier (BTB) effective levels. One such agent
temozolomide is commonly used in
brain tumor patients, which works better when combined with radiation or other
anticancer agents. Likewise,
trastuzumab (
Herceptin, Her-2 inhibitor), which might be effective against Her2/neu over expressing
gliomas may work well when combined with
temozolomide. Nonetheless, both drugs do not cross the BTB to significantly impact patient survival. Beforehand we showed that
potassium channel agonists when intracarotidly administered increased
carboplatin and Her-2 antibody delivery in animal
glioma models by triggering formation of brain vascular endothelial transcytotic vesicles. In this study, we investigated whether, intravenously administered,
ATP-sensitive potassium channel (K(
ATP)) activator (
minoxidil sulfate; MS) increases
temozolomide and
Herceptin delivery to
brain tumors to induce anti-
tumor activity and increase survival in nude mice with
Glioblastoma multiforme (GBM) cells. The results clearly demonstrate that when given intravenously
temozolomide crosses BTB at a relatively low amount while
Herceptin failed to cross the BTB. However, MS co-infusion with [(14)C]-
temozolomide or fluorescently labeled-
Herceptin resulted in improved and selective
drug delivery to
brain tumor. We also showed that combination treatment with
temozolomide and
Herceptin has enhanced anti-
tumor effect which was more prominent than that of either treatment alone in increasing the survival in mice with GBM when co-infused with MS. Therefore,
brain tumor patients may be benefited when anti-neoplastic agent delivery is increased selectively to the
brain tumors using
KATP channel agonists.