title: Reversal of cisplatin resistance in non-small cell lung cancer stem cells by Taxus chinensis var.
abstract: Drug resistance in cells is a major impedance to successful treatment of lung cancer. Taxus chinensis var. inhibits the growth of tumor cells and promotes the synthesis of interleukins 1 and 2 and tumor necrosis factor, enhancing immune function. In this study, T. chinensis var.-induced cell death was analyzed in lung cancer cells (H460) enriched for stem cell growth in a defined serum-free medium. Taxus-treated stem cells were also analyzed for Rhodamine 123 (Rh-123) expression by flow cytometry, and used as a standard functional indicator of MDR. The molecular basis of T. chinensis var.-mediated drug resistance was established by real-time PCR analysis of ABCC1, ABCB1, and lung resistance-related protein (LRP) mRNA, and western blot analysis of MRP1, MDR1, and LRP. Our results revealed that stem cells treated with higher doses of T. chinensis var. showed significantly lower growth inhibition rates than did H460 cells (P < 0.05). The growth of stem and H460 cells treated with a combination of T. chinensis var. and cisplatin was also significantly inhibited (P < 0.05). Rh-123 was significantly accumulated in the intracellular region and showed delayed efflux in stem cells treated with T. chinensis var. (P < 0.05), compared to those treated with verapamil. T. chinensis var.-treated stem cells showed significant downregulation of the ABCC1, ABCB1, and LRP mRNA and MRP1, MDR1, and LRP (P < 0.05) compared to H460 cells. Thus, T. chinensis var.-mediated downregulation of MRP1, MDR1, and LRP might contribute to the reversal of drug resistance in non-small cell lung cancer stem cells.
authors.affiliation: The First People's Hospital of Xiao Shan, Hangzhou, China.
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Jiang
authors.affiliation: The First People's Hospital of Xiao Shan, Hangzhou, China.
authors.forename: X P
authors.initials: XP
authors.lastname: Xu
authors.affiliation: The First People's Hospital of Xiao Shan, Hangzhou, China.
authors.forename: Q M
authors.initials: QM
authors.lastname: Guo
authors.affiliation: The First People's Hospital of Xiao Shan, Hangzhou, China.
authors.forename: X C
authors.initials: XC
authors.lastname: Xu
authors.affiliation: The First People's Hospital of Xiao Shan, Hangzhou, China.
authors.forename: Q Y
authors.initials: QY
authors.lastname: Liu
authors.affiliation: The First People's Hospital of Xiao Shan, Hangzhou, China.
authors.forename: S H
authors.initials: SH
authors.lastname: An
authors.affiliation: The First People's Hospital of Xiao Shan, Hangzhou, China.
authors.forename: J L
authors.initials: JL
authors.lastname: Xu
authors.affiliation: The First People's Hospital of Xiao Shan, Hangzhou, China.
authors.forename: F
authors.initials: F
authors.lastname: Su
authors.affiliation: The First People's Hospital of Xiao Shan, Hangzhou, China jiabintai@163.com.|Zhejiang Chinese Medical University, China jiabintai@163.com.
authors.forename: J B
authors.initials: JB
authors.lastname: Tai
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D004365:Drugs, Chinese Herbal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D020112:Rhodamine 123 / Q000378:metabolism; D015398:Signal Transduction; D020946:Taxus / Q000737:chemistry*; D020394:Vault Ribonucleoprotein Particles / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000099187:Major Vault Protein
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D002945:Cisplatin; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010936:Plant Extracts; D020112:Rhodamine 123; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C513055:ABCB1 protein, human; C421109:multidrug resistance-associated protein 1