title: Platycodin-D Induced Autophagy in Non-Small Cell Lung Cancer Cells via PI3K/Akt/mTOR and MAPK Signaling Pathways.
abstract: Platycodin-D (PD) is an effective triterpene saponin extracted from the root of Platycodon grandiflorum which has been used clinically to treat pulmonary diseases in traditional Chinese medicine. Recently, it has been reported that PD has anti-tumor effects in various cancer models through the induction of apoptosis. However, whether PD induces autophagy in both cell lines and its molecular mechanisms have not been elucidated. Here, our present study confirmed that PD induced autophagy in both NCI-H460 and A549 cells via up-regulating the expression levels of Atg-3, Atg-7 and Beclin-1. Meanwhile, PD contributed to the up-regulation of LC3-II at both protein and mRNA levels. Further detection of the PI3K/Akt/mTOR signaling pathway compared to LY294002 (PI3K kinase inhibitor), RAP (mTOR kinase inhibitor) and insulin (an activator of PI3K/Akt/mTOR signaling pathway) showed that PD induced autophagy through inhibiting the pathway at p-Akt (Ser473), p-p70S6K (Thr389) and p-4EBP1 (Thr37/46) in both cell lines. Moreover, the examination of MAPK signaling pathway showed that PD treatment increased the phosphorylation of JNK and p38 MAPK, while decreased the phosphorylation of Erk1/2 in both cell lines. Additionally, the effects assessed with a panel of pharmacologic inhibitors, including U0126 (Erk1/2 kinase inhibitor), SP600125 (JNK kinase inhibitor) and SB203580 (p38 MAPK kinase inhibitor) suggested that the activation of JNK and p38 MAPK participated in PD-induced autophagy. Taken together, these findings suggested that PD induced autophagy in NCI-H460 and A549 cells through inhibiting PI3K/Akt/mTOR signaling pathway and activating JNK and p38 MAPK signaling pathways. Therefore, PD may be an alternative compound for NSCLC therapy.
authors.affiliation: 1. The Pre-clinical Medicine College, Nanjing University of Chinese Medicine, Nanjing 210023, China ; 2. Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Ruolin
authors.initials: R
authors.lastname: Zhao
authors.affiliation: 2. Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Chen
authors.affiliation: 2. Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Zequn
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: 2. Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Fengming
authors.initials: F
authors.lastname: Zhao
authors.affiliation: 1. The Pre-clinical Medicine College, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Beili
authors.initials: B
authors.lastname: Xi
authors.affiliation: 2. Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 3. Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA ; 4. Department of Hematology & Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Haian
authors.initials: H
authors.lastname: Fu
authors.affiliation: 1. The Pre-clinical Medicine College, Nanjing University of Chinese Medicine, Nanjing 210023, China ; 2. Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Kunfu
authors.initials: K
authors.lastname: Zhou
keywords: MAPK signaling pathways; PI3K/Akt/mTOR; Platycodin-D; autophagy; non-small cell lung cancer