Claudin-7 Mediated Metastasis of Human Lung Adenocarcinoma Cells inIntermittent Hypoxia

Metastasis is a prerequisite for cancer development, which requires both proliferation and migration/invasion of the cancer cells. In this study, we reported that severe hypoxic conditions could inhibit the expression of HIF-1α and Claudin-7 and up-regulate the expression of p18 in human lung adenocarcinoma cells (A-549 cells). We demonstrated that hypoxic conditions can promote the metastasis, while inhibit the viability and proliferation of A-549 cells by downregulating HIF-1α/Claudin-7 and up-regulating p18. However, intermittent hypoxic condition could inhibit A-549 cells invasion and promote cell proliferation by affecting the expression of Claudin-7 and p18. We also confirm, using a small interfering RNA transfection technique (siRNA), that Claudin-7 could act as an anti-cancer biomarker of metastasis in A-549 cells. Silencing HIF-1α in A-549 cells could down-regulate the expression of Claudin-7. Our results suggest that we could use intermittent fluctuations of O2 level in tumor center to inhibit metastasis by controlling the timing and pattern of intermittent hypoxia. It may potentially be used as a new treatment for solid tumors, especially those that are not sensitive to radiotherapy.

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