[The effect of TNP-470 on the proliferation and apoptosis of lung adenocarcinoma cells].
OBJECTIVE
To investigate the effect of TNP-470 on the proliferation and apoptosis of lung adenocarcinoma cells and to explore the mechanism of the effect.


METHODS
The TNP-470 with different concentrations was added to cultured lung adenocarcinoma cell strain AGZY-82A and the expressions of proliferating cell nuclear antigen (PCNA), p53, bcl-2, vascular endothelial growth factor (VEGF) and VEGF receptor Flk-1 of the tumor cells were assessed by immunohistochemical methods.


RESULTS
The experimental data showed that TNP-470 inhibit the expressions of VEGF and Flk-1 by tumor cells with dose-dependence. In the group of cells without TNP-470 (control group) the expression could rates of VEGF and Flk-1 were 70.42% and 50%, respectively; while in the group of cells with 10(7) microgram/L TNP-470, the expression rates of VEGF and Flk-1 decreased to 13.2% and 7.2%, respectively. Under the lnfluence of 10(4) microgram/L TNP-470, the expression rates of VEGF, Flk-1 by the tumor cells decreased gradually with prolonging of the action time. After 6 hours of action, the expression rate of VEGF decreased to 14.4% and after 12 hours, the expression rate of Flk-1 decreased to 6.2%. In the control group the proliferation rate of PCNA-marked cells was (87.03 +/- 0.75)% and the positive expression rate of p53-marked cells was (3.67 +/- 0.39)%, while in the 10(7) microgram/L TNP-470 group the proliferation rate and positive rate of p53-marked cells were 0 and (63.28 +/- 0.84)%, respectively. No expression of bcl-2 in both control and low concentration TNP-470 group. Its expression increased gradually as the concentration induced. In the 10(4) microgram/L TNP-470 group the expression of PCNA by tumor cells decreased. But the expression of p53, bcl-2 increased gradually with prolonging of the action time.


CONCLUSIONS
TNP-470 could inhibit the proliferation and promote the apoptosis of lung adenocarcinoma cells through reduction of the VEGF autocrine and down-regulation of the VEGF receptor.
Ma
Xiaochun
X
Institute of Respiratory Disease, The First Clinical College, China Medical University, Shenyang 110001, China.
Zhang
Ling
L
Kang
Jian
J
Yu
Runjiang
R
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D003510:Cyclohexanes; D015536:Down-Regulation; D016228:Endothelial Growth Factors / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008222:Lymphokines / Q000378:metabolism*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000970:Antineoplastic Agents; D003510:Cyclohexanes; D016228:Endothelial Growth Factors; D008222:Lymphokines; D017978:Receptors, Growth Factor; D012717:Sesquiterpenes; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D000077609:O-(Chloroacetylcarbamoyl)fumagillol