ESTABLISHMENT OF TUMOR SPECIFIC MOLECULER TARGETTING THERAPY AGAINST HYPDXIA INDUCIBLE FACTOR

1.缺氧通过G1期细胞周期逆转诱导口腔癌细胞对5-氟尿嘧啶产生耐药性1）缺氧对口腔鳞癌细胞的存活率无明显影响2）缺氧对NA和SAS细胞的增殖无明显影响，而对HSC-3细胞的增殖无明显影响，3）缺氧敏感细胞（HS）缺氧24 h后HIF-1 α表达增强; 4）缺氧耐受细胞（HR）缺氧24 h后HIF-1 α表达增强。低氧对口腔鳞癌细胞侵袭能力的影响1）Matrigel侵袭实验显示低氧可增强口腔鳞癌细胞的侵袭能力; 2）低氧诱导口腔鳞癌细胞MMP-2的表达，低氧诱导OSCC细胞分泌MMP-9; 4）低氧上调OSCC细胞MMP-2的表达; 5）低氧培养的成纤维细胞条件培养液促进MMP-2的表达。

1.Hypoxia induces resistance to 5-fluorouracil in oral cancer cells via G1 phase cell cycle wrest1) Hypoxia did not affect cell viability of OSCC cells up to 8 hour incubation2) Hypoxia did not affect cell proliferation of NA and SAS, whereas the proliferation ofHSC-3, CA9-22 was down-regulated.3) Hypoxia sensitive cells (HS) display enhanced expression of HIF-1 α within 24 h incubation in hypoxia chamber.4) Hypoxia resistant cells (HR) display constitutive expression of HIF-1α.5) HS showed G1 arrest under the hypoxic condition.6) Enhanced cyto-toxicity of 5-FU was observed in HS.2, Effects of hypoxia on cell invasiveness of OSCC cells1) Hypoxia enhances invasiveness of OSCC cells in Matrigel invasion assay.2) Hypoxia induces expression of MMP-2, MMP-9 of OSCC cells.3) Hypoxia ski induces secretion of MMPs in culture supernatant.4) Activated MMP-2 in OSCC cells was up-regulated by hypoxia5) Fibroblast conditioned medium cultured in hypoxia chamber enhanced MMP-2 expression.