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. HeLa-MDK cells treated with 5-FU, doxorubicin, and cisplatin showed a fold increase in the average IC(50) and an increased cell survival. siRNA-based knockdown of MDK expression in SNU-638 cells decreased the average IC(50) 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.
Kang
Hio Chung
HC
Korean Hereditary Tumor Registry, Cancer Research Institute and Cancer Research Center, Seoul National University, Seoul, South Korea.
Kim
Il-Jin
IJ
Park
Hye-Won
HW
Jang
Sang-Geun
SG
Ahn
Sun-A
SA
Yoon
Sang Nam
SN
Chang
Hee-Jin
HJ
Yoo
Byong Chul
BC
Park
Jae-Gahb
JG
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D000078792:Midkine; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009414:Nerve Growth Factors / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection
D000970:Antineoplastic Agents; C066254:MDK protein, human; D009414:Nerve Growth Factors; D034741:RNA, Small Interfering; D000078792:Midkine; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil