Rosmarinic acid reverses non‐small cell lung cancer cisplatin resistance by activating the MAPK signaling pathway. (27th January 2020)

• Record Type: Journal Article
• Authors: Liao, Xiao‐Zhong; Gao, Ying; Sun, Ling‐Ling; Liu, Jia‐Hui; Chen, Han‐Rui; Yu, Ling; Chen, Zhuang‐Zhong; Chen, Wen‐Hui; Lin, Li‐Zhu
• Is Part Of: Phytotherapy research. Volume 34:Number 5(2020)
• Page Start: 1142
• Page End: 1153
• Publication Date: 2020-01-27
• Subjects: cisplatin -- MAPK -- multidrug resistance -- non‐small cell lung cancer -- rosmarinic acid; Materia medica, Vegetable -- Periodicals; Botany, Medical -- Periodicals; Medicinal plants -- Periodicals; Plant Extracts -- therapeutic use -- Periodicals; Plants, Medicinal -- Periodicals; 581.634
• DOI: 10.1002/ptr.6584
• Languages: English
• ISSNs: 0951-418X

Abstract

Abstract : Cisplatin (DDP) is one of the first‐line chemotherapeutic agents for non‐small cell lung cancer (NSCLC). However, repeated use of cisplatin in clinical practice often induces chemoresistance. The aims of this study were to investigate whether rosmarinic acid (RA) could reverse multidrug resistance (MDR) in NSCLC and to explore the underlying mechanisms. Our data demonstrated that RA significantly inhibited NSCLC cell proliferation and cell colony formation in a dose‐dependent manner, induced G1 phase cell cycle arrest and apoptosis, and increased the sensitivity of cell lines resistant to DDP. Mechanistically, RA inhibited NSCLC cell growth, arrested cell cycle, and induced apoptosis by activating MAPK and inhibiting the expression of P‐gp and MDR1, which correspondingly enhanced p21 and p53 expression. We observed that the growth of xenograft tumors derived from NSCLC cell lines in nude mice was significantly inhibited by combination therapy. We demonstrate that RA is a potentially effective MDR reversal agent for NSCLC, based on downregulation of MDR1 mRNA expression and P‐gp. Together, these results emphasize the putative role of RA as a resistance reversal agent in NSCLC.