Research Papers:

Saikosaponins A, C and D enhance liver-targeting effects of anticancer drugs by modulating drug transporters

Limin Feng, Lijuan Liu, Ya Zhao and Ruizhi Zhao _

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Oncotarget. 2017; 8:110092-110102. https://doi.org/10.18632/oncotarget.22639

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Limin Feng1, Lijuan Liu1, Ya Zhao1 and Ruizhi Zhao1,2

1Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

2Guangdong Province Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou 510006, China

Correspondence to:

Ruizhi Zhao, email: [email protected], [email protected]

Keywords: saikosaponin; Pgp; OCT2; MRP1; MRP2

Received: September 08, 2017     Accepted: October 27, 2017     Published: November 23, 2017


Vinegar-baked Radix Bupleuri (VBRB) is clinically used to enhance the pharmacological activity of drugs used to treat liver diseases. Our previous study demonstrated that this effect is dependent on increased drug accumulation in the liver; however, the underlying mechanism remains unclear. We hypothesize that VBRB mediated its effects by altering drug transporters. Thus, the present study was designed to determine the effects of VBRB’s main components, saikosaponin A, C, and D, on drug transporters. Transporter activity was determined by measuring the intracellular concentration of transporter substrates. Protein and mRNA levels were measured by Western blot and qPCR, respectively. Colchicine was used as the substrate for P-glycoprotein (Pgp) and multidrug resistance protein (MRP) 1, cisplatin was used as the substrate for Mrp2 and organic cation transporters 2 (Oct2), and verapamil and MK571 were used as inhibitors of Pgp and MRP1, respectively. Saikosaponin A, C, and D differentially affected transporter activity. All of the saikosaponins inhibited Pgp activity in Pgp over-expressing HEK293 cells and increased substrate uptake of OCT2 in OCT2 over-expressing HEK293. Saikosaponin C and D inhibited MRP2 activity in HEK293 cells and BRL 3A cell with high MRP2 expression; saikosaponin A increased colchicine accumulation in GSH-stimulated HEK293 cells, but decreased colchicine uptake in HEK293 cells. Saikosaponin D inhibited MRP1 activity in GSH-stimulated HEK293 cells, but marginally affected the uptake of colchicine in HEK293 cells. In conclusion, saikosaponins play a role in VBRB’s induced liver targeting effect through affecting drug transporters with a transporter expression amount depending manner.

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