Expression of PTEN, p27, p21 and AKT mRNA and protein in human BEL-7402 hepatocarcinoma cells in transplanted tumors of nude mice treated with the tripeptide tyroservatide (YSV).
The tripeptide, tyroservatide (YSV), has been previously shown to have antitumor effects through unknown mechanism. In the current study, we examined whether YSV modulates the protumorigenic PI3K pathway in human BEL-7402 hepatocarcinoma cells. BEL-7402 hepatocarcinoma was transplanted into the subcutaneous tissues of nude mice, and YSV, at varying doses, was administered. RT-PCR and Western blot were used to analyze the expression of PTEN, AKT, p21 and p27. YSV at doses of 80 microg/kg/day, 160 microg/kg/day and 320 microg/kg/day markedly inhibited the growth of human BEL-7402 hepatocarcinoma (p < 0.05). YSV increased mRNA and protein expression of the tumor-suppressor genes, PTEN, p21 and p27, and inhibited the mRNA and protein expression of the oncogene AKT. Furthermore, YSV administration was associated with dephosphorylation of both PTEN (which activates PTEN) and AKT (which inhibits AKT). These results are consistent with the possibility that YSV mediates inhibition of tumor growth through inhibition of the PI3K pathway and suggests that YSV should be explored for use as an antitumor agent for hepatocarcinoma.
Zhu
Zhitong
Z
Department of Immunology, Tianjin Medical University, Tianjin 300070, China.
Jia
Jing
J
Lu
Rong
R
Lu
Yi
Y
Fu
Zheng
Z
Zhao
Lan
L
Wang
Li
L
Jin
Mengjue
M
Zhao
Lin
L
Gao
Wenyuan
W
Yao
Zhi
Z
D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
D050759:Cyclin-Dependent Kinase Inhibitor p21; D047908:Intracellular Signaling Peptides and Proteins; D009842:Oligopeptides; D012333:RNA, Messenger; C510683:tripeptide tyroservatide; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase