간암세포에서 저산소증에 의해 유도되는 VEGF의 발현기작에 대한 연구 = Studies on the Mechanism of Hypoxic Increase of VEGF Expression in the Hep3B Human Hepatoma Cells

다국어 초록 (Multilingual Abstract)

Purpose: Hepatocellular carcinoma(HCC),a typical hypervasculized tumor is very sensitive to hypoxia and vascular endothelial growth factor(VEGF) has previously been identified to be up-regulated in response to hypoxia in several cell types. However, the molecular mechanisma by which hypoxia is sensed by the cells remain enigmatic. To investigate whether calcium and AP-1 are involved in hypoxia-sensing mechanism, we performed following eaperiments.
Materials and Methods: Hep3B cells were grown in hypoxia condition. To assess cell viability, MTT assay was performed. To investigate the effect of calcium and AP-1,northern blot analysis was performed after treatment with BAPTA/AM.
Results: The expression of VEGF was significantly up-regulated by hypoxia in Hep3B, hepatocellular carcinoma cell line. The increased expression of VEGF induced by hypoxia was blocked by the addition of BAPTA/AM, a cytosolic calcium chelator to the media. In addition, we found that the expression of c-jun protooncogene was also-regulated by hypoxia. Hypoxia increase of c-jun expression was also normalized by the treatment with BAPTA/AM.
Conclusion: These results suggest that the increased expression of VEGF by hypoxia is mediated through the calcium and c-jun signalling pathway in the Hep3B human hepatoma cell lines.