title: Steroidal saponin of Trillium tschonoskii. Reverses multidrug resistance of hepatocellular carcinoma.
abstract: Combating with multidrug resistance (MDR) is a major part of hepatocellular carcinoma (HCC) chemotherapy. Steroidal saponin from Trillium tschonoskii (TTS) could be a potential weapon. We found TTS could reverse the MDR in HCC cells and significantly enhance chemosensitization. TTS inhibited HepG2 and R-HepG2 cells survival in a dose-dependent manner by 75% and 76%, respectively (p<0.01), as well as colony formation 77% and 81% (p<0.01). Moreover, TTS induced sensitization of R-HepG2 to anti-cancer drugs, indicated by significantly reduced IC50. On the other hand, TTS suppressed expression of P-glucoprotein in MDR HCC cells, and thereby increased accumulation of doxorubicin from 126 ng/10(5)cells to 752 ng/10(5)cells (p<0.01). TTS also repressed expression of many other MDR genes, such as MRP1, MRP2, MRP3, MRP5, MVP and GST-π. In vivo, TTS dose-dependently reduced R-HepG2 cells xenografts tumour formation by inhibiting tumour cells proliferation in mice. Consistence with in vitro finding, TTS induced R-HepG2 sensitization to doxorubicin and therefore reduced tumour formation in vivo.
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi Province 710032, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Zhai
authors.forename: Nanlin
authors.initials: N
authors.lastname: Li
authors.forename: Haifeng
authors.initials: H
authors.lastname: Jin
authors.forename: Jianghao
authors.initials: J
authors.lastname: Chen
authors.forename: Shifang
authors.initials: S
authors.lastname: Yuan
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Juliang
authors.initials: J
authors.lastname: Zhang
authors.forename: Yongping
authors.initials: Y
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Yun
authors.forename: Jing
authors.initials: J
authors.lastname: Fan
authors.forename: Jun
authors.initials: J
authors.lastname: Yi
authors.forename: Rui
authors.initials: R
authors.lastname: Ling
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000378:metabolism / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008807:Mice, Inbred BALB C; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D013256:Steroids / Q000494:pharmacology / Q000627:therapeutic use; D031446:Trillium / Q000737:chemistry*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004317:Doxorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010936:Plant Extracts; D012503:Saponins; D013256:Steroids
keywords: Chemotherapy; Hepatocellular carcinoma; Multidrug resistance; Saponin; Trillium tschonoskii