Oroxylin A reverses CAM-DR of HepG2 cells by suppressing Integrinβ1 and its related pathway.
Oroxylin A, a naturally occurring monoflavonoid extracted from Scutellariae radix, shows effective anticancer activities and low toxicities both in vivo and in vitro in previous studies. In this study, we investigated whether the CAM-DR model of HepG2 cells showed resistance to cytotoxic agents compared with normally cultured HepG2 cells. Furthermore, after the treatment of Paclitaxel, less inhibitory effects and decreased apoptosis rate were detected in the model. Data also revealed increased expression of Integrinβ1 might be responsible for the resistance ability. Moreover, Integrinβ1-siRNA-transfected CAM-DR HepG2 cells exhibited more inhibitory effects and higher levels of apoptosis than the non-transfected CAM-DR cells. The data corroborated that Integrinβ1 played a significant role in CAM-DR. After the treatment of weakly-toxic concentrations of Oroxylin A, the apoptosis induced by Paclitaxel in the CAM-DR model increased dramatically. Western blot assay revealed Oroxylin A markedly down-regulated the expression of Integrinβ1 and the activity of related pathway. As a conclusion, Oroxylin A can reverse the resistance of CAM-DR via inhibition of Integrinβ1 and its related pathway. Oroxylin A may be a potential candidate of a CAM-DR reversal agent.
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
Binbin
B
Zhu
Li
L
Zhao
Litao
L
Zhu
Hu
H
Wang
Yunying
Y
Sha
Jing
J
Yao
Zhiyu
Z
Li
Qidong
Q
You
Qinglong
Q
Guo
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002448:Cell Adhesion; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005419:Flavonoids / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D019012:Integrin beta1 / Q000187:drug effects* / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D031364:Scutellaria baicalensis / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D019012:Integrin beta1; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; D017239:Paclitaxel