Tas13D inhibits growth of SMMC-7721 cell via suppression VEGF and EGF expression.
OBJECTIVE
Taspine, isolated from Radix et Rhizoma Leonticis has demosntrated potential proctiective effects against cancer. Tas13D, a novel taspine derivative synthetized by structure-based drug design, have been shown to possess interesting biological and pharmacological activities. The current study was designed to evaluate its antiproliferative activity and underlying mechanisms.


METHODS
Antiproliferative activity of tas13D was evaluated by xenograft in athymic mice in vivo, and by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and cell migration assays with human liver cancer (SMMC-7721) cell lines in vitro. Docking between tas13D and VEGFR and EGFR was studied by with a Sybyl/Surflex module. VEGF and EGF and their receptor expression was determined by ELISA and real-time PCR methods, respectively.


RESULTS
Our present study showed that tas13D inhibited SMMC-7721 xenograft tumor growth, bound tightly with the active site of kinase domains of EGFR and VEGFR, and reduced SMMC-7721 cell proliferation (IC=34.7 μmol/L) and migration compared to negative controls. VEGF and EGF mRNAs were significantly reduced by tas13D treatment in a dose-dependent manner, along with VEGF and EGF production.


CONCLUSIONS
The obtained results suggest that tas13D inhibits tumor growth and cell proliferation by inhibiting cell migration, downregulating mRNA expression of VEGF and EGF, and decreasing angiogenic factor production. Tas13D deserves further consideration as a chemotherapeutic agent.
School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Huai-Zhen
HZ
He
Nan
N
Wang
Jie
J
Zhang
Lei
L
Zheng
Yan-Min
YM
Zhang
D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D000470:Alkaloids; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; C018394:taspine