title: Astragaloside IV inhibits migration and invasion in human lung cancer A549 cells via regulating PKC-α-ERK1/2-NF-κB pathway.
abstract: 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.
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu 210046, China; Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu 210028, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Cheng
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu 210046, China; Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu 210028, China.
authors.forename: Junfei
authors.initials: J
authors.lastname: Gu
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu 210028, China; College of Pharmacy, Jiangsu University, Jiangsu 212013, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu 210046, China; College of Pharmacy, Jiangsu University, Jiangsu 212013, China.
authors.forename: Jiarui
authors.initials: J
authors.lastname: Yuan
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu 210046, China; Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu 210028, China.
authors.forename: Bingjie
authors.initials: B
authors.lastname: Zhao
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu 210046, China; Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu 210028, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu 210046, China; Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu 210028, China; College of Pharmacy, Jiangsu University, Jiangsu 212013, China. Electronic address: jxiaobin2005@hotmail.com.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Jia
mesh_terms: D027885:Astragalus propinquus; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D004365:Drugs, Chinese Herbal; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011493:Protein Kinase C / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D016326:Extracellular Matrix Proteins; D018836:Inflammation Mediators; D016328:NF-kappa B; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; C027492:Huang Qi; D011493:Protein Kinase C
keywords: Astagaloside IV; Inflammatory response; Invasion; Lung cancer; Migration