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

• Astragaloside IV could inhibit the adhesion, migration and invasion of A549 cells.
• Astragaloside IV inhibited A549 cells migration and invasion by PKC-α-ERK1/2-NF-κB pathway.
• The inflammation cytokines were involved in the regulation of A549 cells migration and invasion by astragaloside IV.

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.