Astragaloside IV inhibits migration and invasion in human lung cancer A549 cells via regulating PKC-α-ERK1/2-NF-κB pathway

The migration and invasion characteristics that are related to inflammatory response play important roles in the development of lung cancer. Astagaloside IV (AS-IV), an effective saponin component isolated from Astragali Radix, has been reported to inhibit metastasis of tumor cells. However, little is known about the underlying mechanism of AS-Non inhibiting the migration and invasion characteristics of lung cancer cells. In the present study, cell proliferation was assessed by MIT colorimetric assay. Wound-healing assay and transwell chambers assay were used to detect the effects of AS-IV on the migration capacity and invasiveness of A549 cells. Metastasis-related bio-markers expressions were detected by Western blot analysis. Levels of inflammatory factors including transforming growth factor-beta 1 (TGF-beta 1), tumor necrosis factor-a (TNF-alpha) and interleukin-6 (IL-6) in cell supernatant were tested by enzyme linked immunosorbent assay (ELISA). The expressions of PKC-alpha, ERK1/2 and NF-kappa B were analyzed by Western blot analysis. The results showed that the migration and invasion ability of A549 has been suppressed in presence of AS-IV. The levels of MMP-2, MMP-9 and integrin beta 1 were decreased significantly, whereas E-cadherin was increased by the treatment of different concentrations AS-IV. Furthermore, AS-IV also significantly decreased TGF-beta 1, TNF-a and IL-6 levels. Interestingly, PKC pathway inhibitor AEB071 (Sotrastaurin) (0.1 mu M) or ERK inhibitor U0126 (1 mu M) or NF-kappa B inhibitor PDTC (1 mu M) could affect suppression of AS-IV on cell invasion, at least partially. Our results suggested that the migration and invasion of AS-IV in A549 cells might be related to the PKC-alpha-ERK1/2-NF-kappa B pathway. The result indicated that AS-IV could be used as a candidate for the inhibition of metastasis of human lung cancer. (C) 2014 Elsevier B.V. All rights reserved.