Linarin inhibits radiation-induced cancer invasion by downregulating MMP-9 expression via the suppression of NF-κB activation in human non-small-cell lung cancer A549
Radiotherapy is routinely used in the treatment of lung cancer patients. However, it often causes malignant effects, such as promoting cancer cell migration and invasion. Previous studies demonstrated that ionizing radiation (IR) promotes cancer cell invasion by stimulating the β-catenin, IL-6, STAT3, and Bcl-XL signaling pathway or the PI3K, Akt, and NF-κB signaling pathway. Both Bcl-XL and NF-κB stimulate the secretion of matrix metalloproteases (MMPs), including MMP-2 and MMP-9. In the present study, linarin isolated from Chrysanthemum morifolium flowers significantly decreased the IR-induced cell migration and invasion at a concentration of 5 μM in A549 cells. This effect was mediated via MMP-9 downregulation and the suppression of NF-κB activation by inhibiting NF-κB and IκB-α phosphorylation. However, linarin did not affect the STAT3/Bcl-XL pathway or the stabilization of β-catenin. Overall, these results suggest that linarin repressed the MMP-9-dependent invasion pathway by regulating NF-κB activity, thereby inhibiting IR-induced cancer metastasis.