Astragaloside IV enhances cisplatin chemosensitivity in hepatocellular carcinoma by suppressing MRP2

• Published in: European journal of pharmaceutical sciences Vol. 148; p. 105325
• Main Authors: Qu, Xiaoyu, Gao, Huan, Zhai, Jinghui, Sun, Jingmeng, Tao, Lina, Zhang, Yueming, Song, Yanqing, Hu, Tingting
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.05.2020
• Subjects: Animals; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Astragaloside IV; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell Proliferation - drug effects; Chemosensitivity; Cisplatin; Cisplatin - pharmacology; Drug Interactions; Drug Resistance, Neoplasm - drug effects; Hep G2 Cells; Hepatocellular carcinoma; Humans; Kidney - drug effects; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Mice; Mice, Inbred BALB C; Multidrug resistance-associated protein 2; Multidrug Resistance-Associated Proteins - metabolism; Saponins - pharmacology; Triterpenes - pharmacology; Chemosensitivity; Hepatocellular carcinoma; Astragaloside IV; Cisplatin; Multidrug resistance-associated protein 2
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2020.105325

•AS IV could enhance the chemosensitivity of cisplatin in HepG2 cells.•AS IV could enhance anti-tumor effect of cisplatin in H22 tumor-bearing mice.•AS IV may play the role of chemosensitivity by supressing MRP2 in tumor cells.•MRP2 in mice kidneys were not altered and not influenced in kidney function. Decreased chemosensitivity among tumor cells is often an obstacle in cisplatin (Cis) chemotherapy. Overexpression of multidrug resistance-associated protein 2 (MRP2) is a key mechanism underlying decreased Cis chemosensitivity and resistance. Astragaloside IV (AS IV) is an important component derived from the well-known traditional Chinese herb Astragalus membranaceus. The aim of this study was to explore the role of AS IV in enhancing the antitumor effect of Cis by suppressing MRP2 expression in HepG2 cells and H22 tumor-bearing mice. After co-treatment of HepG2 cells with Cis and AS IV, we assessed the effects on cell proliferation and apoptosis. Tumor growth and apoptosis assessment were performed to assess chemosensitivity in H22 tumor-bearing mice. We used western blotting, immunofluorescence assays, and immunohistochemistry assays to detect MRP2 expression in HepG2 cells, H22 tumor tissues and mouse kidney tissues. AS IV enhanced Cis chemosensitivity by increasing tumor cell apoptosis and slowing tumor growth in vitro and in vivo. MRP2 overexpression in tumor cells was induced by Cis, which contributes to decreased chemosensitivity and Cis resistance. Co-administration of AS IV suppressed MRP2 expression in tumor tissues, which might be an important mechanism for enhancing Cis chemosensitivity in hepatocellular carcinoma. Moreover, AS IV alleviated Cis-induced kidney injury in mice without changing MRP2 expression. In total, AS IV enhanced the antitumor effect of Cis against hepatocellular carcinoma by suppressing MRP2 expression in tumor cells. The results provide a new insight into the combined use of a chemotherapy drug and natural ingredients to treat cancer. [Display omitted]