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-IV on inhibiting the migration and invasion characteristics of lung cancer cells. In the present study, cell proliferation was assessed by MTT 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-β1 (TGF-β1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cell supernatant were tested by enzyme linked immunosorbent assay (ELISA). The expressions of PKC-α, ERK1/2 and NF-κB 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 β1 were decreased significantly, whereas E-cadherin was increased by the treatment of different concentrations AS-IV. Furthermore, AS-IV also significantly decreased TGF-β1, TNF-α and IL-6 levels. Interestingly, PKC pathway inhibitor AEB071 (Sotrastaurin) (0.1 μM) or ERK inhibitor U0126 (1 μM) or NF-κB inhibitor PDTC (1 μM) 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-α-ERK1/2-NF-κB pathway. The result indicated that AS-IV could be used as a candidate for the inhibition of metastasis of human lung cancer.