induces apoptosis and prevents angiogenesis with bevacizumab in colon cancer through direct inhibition of / via under hypoxia.

Angiogenesis and antiapoptosis effects are the major factors influencing malignancy progression. Hypoxia induces multiple mechanisms involving microRNA (miRNA) activity. Vascular endothelial growth factor (VEGF) is correlated with angiogenesis. An antiapoptotic factor, myeloid leukemia 1 (Mcl-1) is the main regulator of cell death. This study examined the role of in inhibiting VEGF and Mcl-1 secretion by directly targeting by downregulating under hypoxia. The protein expression of ROCK1 or Met/HIF-1α/Mcl-1 in HCT116 and HT29 cells (all < 0.05) was significantly reduced by . The tube-formation assay revealed that significantly suppressed angiogenesis and synergistically enhanced the effects of bevacizumab (both < 0.05). The MTT assay revealed the inhibitory ability of in HCT116 and HT29 cells (both < 0.05). and bevacizumab exerted synergistic antitumorigenic effects ( < 0.05) in an animal model. Serum expression of metastatic colorectal cancer (mCRC) patients with a partial response was higher than that of mCRC patients with disease progression ( = 0.026). This result revealed that downregulated and by directly targeting to decrease angiogenesis and increase the apoptosis of colon cancer cells. Furthermore, serum levels have prognostic/predictive value in patients with mCRC receiving bevacizumab.