The Studys Of Inhibition Of Arsenic Trioxide On Angiogenesis In Breast Carcinoma And Its Mechanism

PART ONE THE EFFECT OF HYPOXIA-INDUCIBLE FACTOR-1αON THE ANGIOGENESIS AND PROGRESSION IN BREAST CARCINOMA SECTION ONE CORRELATION BETWEEN EXPRESSION OF HYPOXIA-INDUCIBLE FACTOR-1α AND ANGIOGENESIS IN BREAST NEOPLASM Objective: To investigate the expression of hypoxia-inducible factor-1α(HIF-1α) and vascular endothelial growth factor(VEGF) and microvessel density(MVD) in breast neoplasm,and to analysis their correlations and clinical significance in breast carcinoma. Methods:Expressions of HIF-1α and VEGF in 34 breast carcinoma specimens and 12 normal breast tissues were detected in mRNA level by RT-PCR analysis and detected by Western blot in protein level. Expressions of HIF-1 α and VEGF and MVD in 48 breast carcinoma specimens were tested by immunohistochemistry in protein level. Breast neoplasm;Hypoxia -inducible factor-1α(HIF-1α);VEGF; MVD Breast carcinoma;HIF-1α; CarcinogenesisHypoxia;Breast neoplasm;VEGF; HIF-1αLINE Objective: To investigate the effect of hypoxia on vascular endothelial growth factor expression in breast carcinoma cell line(MDA-MB-435S) and the effect of As2O3 on VEGF expression and its mechanism. Methods: Hypoxia culture mode in vitro was established in MDA-MB-435S cells line. After cultured in hypoxia circumstance for 12 hours and intervened by As2O3 ,expressions of VEGF and hypoxia-inducible factor-1α(HIF-1α)were identified in protein level by Western blot analysis,and expressions of VEGF mRNA and HIF-1α mRNA were detected by RT-PCR. The effect of As2O3 on survivor of cells was tested by MTT analysis. Results: As2O3 in low concentration had little effect on cells survivor,but As2O3 in high concentration decreased significantly the survivor of cells. As2O3 in different concentration had little effect on VEGF expression in cells cultured under normoxia,but had significant effect on cells cultured under hypoxia circumstance. Also, As2O3 can decreased the expression of HIF-1α protein by 70%,but showed little effect on HIF-1α mRNA.Dithiothreitol(DTT)can partly block the effect of As2O3 on HIF-1αand VEGF. Conclusion: Expression of VEGF in breast carcinoma cells can be inhibited by arsenic trioxide,which may be involving the transcription factor HIF-1α.