Antitumor activity of F90, an epidermal growth factor receptor tyrosine kinase inhibitor, on glioblastoma cell line SHG-44.
BACKGROUND
Over-expression of epidermal growth factor receptor (EGFR) is thought to be related to cell proliferation, invasion, metastasis, resistance to chemoradiotherapy and poor prognosis of various human cancers. Forty percent to fifty percent of glioblastoma multiforme (GBM) possess deregulated EGFR, which may contribute to the aggressive and refractory course of GBM. Therefore, blockade of EGFR signal transduction may be a promising treatment strategy for GBM.


METHODS
MTT assay, cell growth curve assay and tumor xenograft model were used to evaluate the antitumor activity of F90 against SHG-44 in vitro and in vivo. Western blot assay was applied to evaluate the expression of p-EGFR, p-ERK1, p-JNK, p-P38, Bcl2 and P53 proteins.


RESULTS
F90 inhibited the cell proliferation in a dose-dependent manner in vitro. The growth of SHG-44 tumor xenografts was suppressed by F90 at a high dose level (100 mg x kg(-1) x d(-1)). Phosphorylation of EGFR and activated downstream signaling proteins, such as ERK1, JNK and P38, were found to be depressed after incubation with F90 for 48 hours in vitro. Down-regulated Bcl2 protein and up-regulated P53 protein were also observed.


CONCLUSIONS
The results demonstrate that F90 is effective in inhibiting the proliferation of SHG-44 cells in vitro and tumor growth in vivo, suggesting that F90 may be a new therapeutic option for treatment of GBM.
Liu
Fang-Jun
FJ
Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
Gui
Song-Bai
SB
Li
Chu-Zhong
CZ
Sun
Ze-Lin
ZL
Zhang
Ya-Zhuo
YZ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011799:Quinazolines / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000970:Antineoplastic Agents; C533668:F90 compound; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011799:Quinazolines; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors