Hokudai University. Japan: The antiarrhythmic agent verapamil was found to inhibit the drug resistance in tumor blood vessel cells. (Tumor Endothelial Cells: TECs). Verapamil improves the anti-cancer effect of Paclitaxel by inhibiting the transporter in TECs. Combination therapy with verapamil and the anti-cancer drug paclitaxel enhanced the inhibitory effects on tumor growth and metastasis in vivo. The possibility of expanded applications of existing drugs for cancer therapy which target tumor blood vessels was demonstrated.
Recently, Researcher Kosuke Akiyama, Project Associate Professor
Kyoko Hida and others reported that the resistance to anticancer drugs
is present not only in cancer cells, but also in tumor endothelial cells
(TECs)1). In this study, it was found that by inhibiting ABC transporter2) in TECs, the antiarrhythmic agent verapamil inhibits TEC’s resistance to the anti-cancer drug paclitaxel3),
and as a result, improving its therapeutic effect. In therapy
experiments using mice, a combination of verapamil and a low dose of the
anti-cancer drug paclitaxel4) was found to
provide anti-tumor and inhibitory effects on cancer metastasis that
could not be obtained with paclitaxel alone. The discovery that these
results were attributable to anti-angiogenetic effects is a first in the
world.
1) Tumor Endothelial Cells: TEC
Thin, flat cells that line the interior surface of blood vessels are
called vascular endothelial cells. In comparison with the endothelial
cells in normal blood vessels, TECs lining the blood vessels in tumor
tissues are reported to have molecular-biologically different
characteristics such as the acceleration of specific gene expressions.
2) ABC Transporter
A membrane transporter which transports substances using ATP energy.
P-glycoprotein (P-gp) is well-known as a drug-resistant related
molecular transporter, and functions to discharge specific drugs from
inside the cell to outside the cell. In cancer cells, its correlation
between p-gp upregulation and drug-resistance has been reported.
3) Paclitaxel
An anti-cancer agent belong to the taxane family. Paclitaxel inhibits
cancer cell division by bonding to cell microtubule and stabilizing it,
and inhibiting depolymerization.
4) Verapamil
A calcium channel inhibitor to control the aperture of the membrane
calcium channel. It is generally used as an anti-arrhythmic drug.
Moreover, it is known as inhibitor to block P-gp function.