Regulation of MDK expression in human cancer cells modulates sensitivities to various anticancer drugs:: MDK overexpression confers to a multi-drug resistance

MDK is a heparin-binding growth factor associated with cancer development. Here, we sought to examine the association of MDK expression with resistance and sensitivity to different chemotherapeutic agents. We established stable HeLa cell transfectants (HeLa-MDK) and tested for decreased sensitivity to chemotherapeutic agents (5-FU, doxorubicin, and cisplatin). In addition, we used siRNA to block MDK expression in SNU-638 human gastric cancer cells and examined the chemosensitizing effect. HeLaMDK cells treated with 5-FU, doxorubicin, and cisplatin showed a fold increase in the average IC50 and an increased cell survival. siRNA-based knockdown of MDK expression in SNU-638 cells decreased the average IC50 by 18-44% in cells treated with three drugs. Further investigations on the molecular mechanism should be clarified, but these results indicate that MDK up- and down-regulation appears to be capable of changing the chemosensitivities of cancer cells and MDK may have possible importance as a candidate therapeutic molecule. (c) 2006 Elsevier Ireland Ltd. All rights reserved.