Aim: To investigate the effects of HIF-1α by RNAi on invasion and metastasis of esophageal carcinoma Eca109 cells in vitro and in vivo, in order to explore its probable mechanism.
Methods: CoCl(2); was used to mimic tumor hypoxic microenvironment. mRNA and protein levels of HIF-1α, E-cadherin and MMP-2 under hypoxia were detected by RT-PCR and immunohistochemistry. The effects of silencing HIF-1α by RNAi on HIF-1α, E-cadherin and MMP-2 mRNA were detected by RT-PCR. The effect of RNAi on invasion and metastasis were tested by cell scratch assay and transwell chambers. The Eca109-implanted nude mouse model was established, and the effects of HIF-1αon tumor growth and lymphoid node metastasis were observed. The expressions of HIF-1α, E-cadherin and MMP-2 in transplanted tumors were detected by Western blot, and the effects of HIF-1α on tumor growth, invasion and metastasis in vitro and in vivo were analyzed.
Results: Hypoxia up-regulated HIF-1α protein, mRNA and protein levels of E-cadherin down-regulated, and MMP-2 up-regulated, while had no effect on HIF-1α mRNA . RNAi could silencing HIF-1α effectively, and inhibited E-cadherin or MMP-2 decreased or increased, respectively. The migration and the number of invading cells decreased (P<0.05) after silencing HIF-1α by RNAi. The tumor volume was much smaller, lymph node metastasis rate lower as well in vivo (P<0.05).
Conclusion: Via its effects on E-cadherin and MMP-2, HIF-1α regulate the growth, invasion and metastasis of Eca109 cells in vitro and in vivo.