title: Vitamin E reverses multidrug resistance in vitro and in vivo.
abstract: Multidrug resistance (MDR) is a major obstacle to successful and effective chemotherapeutic treatments of cancers. This study explored the reversal effects of vitamin E on MDR tumor cells in vitro and in vivo, elucidating the potential mechanism of this reversal. VE at a concentration of 50 μM exhibited a significant reversal of the MDR effect (compared to only PTX in DMSO, p<0.05) in two human MDR cell lines (H460/taxR and KB-8-5). The MDR cell xenograft model was established to investigate the effect of VE on reversing MDR in vivo. Mice intravenously injected with Taxol (10 mg/kg) with VE (500 mg/kg, IP) showed an ability to overcome the MDR. VE and its derivatives can significantly increase intracellular accumulation of rhodamine 123 and doxorubicin (P-gp substrate), but not alter the levels of P-gp expression. These treatments also did not decrease the levels of intracellular ATP, but were still able to inhibit the verapamil-induced ATPase activity of P-gp. The new application of VE as an MDR sensitizer will be attractive due to the safety of this treatment.
authors.affiliation: School of Pharmacy, Harbin Medical University, Harbin 150086, PR China.
authors.forename: Jingling
authors.initials: J
authors.lastname: Tang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.forename: Kelly
authors.initials: K
authors.lastname: Racette
authors.forename: Dun
authors.initials: D
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000975:Antioxidants; D014810:Vitamin E; D000255:Adenosine Triphosphate; D017239:Paclitaxel