Marked suppression of tumor growth by FTY720 in a rat liver tumor model: the significance of down-regulation of cell survival Akt pathway.
We aim to investigate the anticancer effect of a novel immunomodulator FTY720 on a rat orthotopic liver tumor model. A buffalo rat orthotopic liver tumor model was established by injection of a buffalo hepatoma cell line MH7777 into the right portal vein. FTY720 was administered by intraperitoneal injection starting at 10 days after tumor cell injection at a dosage of 5 mg/kg/day. FTY720 markedly suppressed tumor growth and inhibited tumor progression by selective induction of apoptosis of tumor cells via down-regulation of phospho-Akt(ser473) and up-regulation of cleaved caspase-3, together with decrease of focal adhesion kinase. Moreover, the proliferation index of tumor cells was significantly reduced to 15.92+/-5.03% by FTY720 compared with that of 42.92+/-4.47% in the control group (p<0.001). In addition, we confirmed that FTY720 caused no effect on infiltrated lymphocyte in tumor tissue. We conclude that FTY720 is an effective anticancer agent for liver tumor in a rat model without affecting the immune system of the host.
Ng
Kevin T
KT
Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, PR China.
Man
Kwan
K
Ho
Joanna W
JW
Sun
Chris K
CK
Lee
Terence K
TK
Zhao
Yi
Y
Lo
Chung Mau
CM
Poon
Ronnie T
RT
Fan
Sheung Tat
ST
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D018450:Disease Progression; D015536:Down-Regulation; D000068876:Fingolimod Hydrochloride; D015972:Gene Expression Regulation, Neoplastic; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D009368:Neoplasm Transplantation; D011409:Propylene Glycols / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015854:Up-Regulation
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D051057:Proto-Oncogene Proteins c-akt; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine