A 20(S)-protopanaxadiol derivative PPD12 reverses ABCB1-mediated multidrug resistance with oral bioavailability and low toxicity

doi:10.3892/ol.2018.9338

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	A 20(S)-protopanaxadiol derivative PPD12 reverses ABCB1-mediated multidrug resistance with oral bioavailability and low toxicity
	Wei, Shunfeng 1,2; Chen, Wantao 1; Hu, Lihong 3; Pan, Jinsong 2; Wang, Xu 1
刊名	ONCOLOGY LETTERS
	2018-11
卷号	16 期号:5 页码:5891-5899
关键词	multidrug resistance ATP-binding cassette subfamily B member 1 toxicity pharmacokinetics
ISSN号	1792-1074
DOI	10.3892/ol.2018.9338
文献子类	Article
英文摘要	The ATP-binding cassette subfamily B member 1 (ABCB1) is a transporter that mediates multidrug resistance (MDR) against chemotherapy, which leads to decreased patient survival. To inhibit ABCB1 activity in MDR cancer cells, the authors previously designed and synthesized a derivative from 20(S)-protopanaxadiol (PPD) PPD12 and verified its efficacy in ABCB1-overexpressing cancer cells. In the present study, the reversal effect of PPD12 on MDR was further evaluated and its pharmacokinetics and toxicity in vitro and in vivo were investigated. Incubation with PPD12 may significantly ameliorate the drug resistance of KB/VCR cells in a short time and maintain its reversed MDR ability for increasing time periods. In assays on a series of CYP450 activities, PPD12 demonstrated slight inhibition effects on the majority of enzymes. The bioavailability of PPD12 was nearly 100% by oral administration in a mouse model. Single PPD12 oral gavage at either high doses or subchronic low doses, was well tolerated by the mice. In addition, PPD12 at the therapeutic dosage did not significantly increase the toxicity of the chemotherapeutic agent Adriamycin when mice received a combination of the two compounds. In conclusion, PPD12 represents a novel type of ABCB1 inhibitor that has significant bioactivity in terms of MDR, high oral bioavailability and low toxicity.
资助项目	Project of the Shanghai Science and Technology Committee[14431905800]
WOS关键词	F9 TERATOCARCINOMA CELLS ; HERB-DRUG INTERACTIONS ; IN-VITRO ; CARDIAC DYSFUNCTION ; ESTROGEN-RECEPTOR ; LIVER-MICROSOMES ; CHILDHOOD-CANCER ; CLINICAL-TRIALS ; GINSENG ; GINSENOSIDES
WOS研究方向	Oncology
语种	英语
出版者	SPANDIDOS PUBL LTD
WOS记录号	WOS:000448433500048
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279516]
专题	上海中药现代化研究中心
通讯作者	Pan, Jinsong; Wang, Xu
作者单位	1.Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Oral & Maxillofacial Head & Neck Oncol, Sch Med, 639 Zhizaoju Rd, Shanghai 200011, Peoples R China; 2.Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Stomatol, Sch Med, 85 Wujin Rd, Shanghai 200080, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Res Ctr Modernizat Tradit Chinese Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wei, Shunfeng,Chen, Wantao,Hu, Lihong,et al. A 20(S)-protopanaxadiol derivative PPD12 reverses ABCB1-mediated multidrug resistance with oral bioavailability and low toxicity[J]. ONCOLOGY LETTERS,2018,16(5):5891-5899.
APA	Wei, Shunfeng,Chen, Wantao,Hu, Lihong,Pan, Jinsong,&Wang, Xu.(2018).A 20(S)-protopanaxadiol derivative PPD12 reverses ABCB1-mediated multidrug resistance with oral bioavailability and low toxicity.ONCOLOGY LETTERS,16(5),5891-5899.
MLA	Wei, Shunfeng,et al."A 20(S)-protopanaxadiol derivative PPD12 reverses ABCB1-mediated multidrug resistance with oral bioavailability and low toxicity".ONCOLOGY LETTERS 16.5(2018):5891-5899.