Study on the regulation of anticancer agent-resistance by sphingolipids in melanoma cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590185
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Gifu University
• Principal Investigator: SEISHIMA MARIKO 岐阜大学, 医学(系)研究科(研究院), 教授 (00171314)
• Co-Investigator(Kenkyū-buntansha): KANOH Hiroyuki 岐阜大学, 医学系研究科, 准教授 (40566494) ; BANNO Yoshiko 岐阜大学, 医学系研究科, 非常勤講師 (50116852)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: sphingosine kinase 1 / sphingosine 1-phosphate / FTY720 / melanoma / cisplatin

Outline of Final Research Achievements

Sphingosine kinase (SK), a key enzyme in sphingosine-1-phosphate (S1P) synthesis, is known to be overexpressed in various cancer cells. The effects of anti-cancer agents on SK1/S1P signaling have not been fully assessed in melanoma cells. We investigated the effects of combination of FTY720, an S1P receptor antagonist, and cisplatin, an anti-cancer drug, on cell viability and molecular mechanisms in human melanoma line, SK-Mel-28 cells. By combination of FTY720 and cisplatin, the viability of melanoma cells was reduced, and expression of apoptosis-associated cleaved-PARP was significantly enhanced. In addition, combination of FTY720 and cisplatin reduced SK1 expression and also reduced the expression of phosphorylated PI3K, Akt, and mTOR. These findings suggest that FTY720 and cisplatin synergistically induce cell death and apoptosis through downregulation of the PI3K/Akt/mTOR pathway in SK-Mel-28 cells.

Free Research Field

皮膚科学