title: Tetrandrine prevents multidrug resistance in the osteosarcoma cell line, U-2OS, by preventing Pgp overexpression through the inhibition of NF-κB signaling.
abstract: The development of multidrug resistance (MDR) remains a major limitation to successful chemotherapy in osteosarcoma. Preventing the introduction of MDR has been a research hotspot in clinical and investigational oncology. The aim of this study was to evaluate the preventive effects of tetrandrine (TET) against MDR in osteosarcoma. For this purpose, U-2OS human osteosarcoma cells were treated with paclitaxel alone or a combination of paclitaxel with TET. The cells treated with paclitaxel alone eventually acquired MDR along with the overexpression of and highly activated P-glycoprotein (Pgp), while the cells treated with the paclitaxel-TET combination were sensitive to chemotherapeutic drugs and expressed decreased levels of Pgp and less Pgp activity. The promoter activities of MDR gene 1 (MDR1) and nuclear factor (NF)‑κB, and the expression levels of NF-κB and p-IκB-α were all enhanced in the cells cultured with paclitaxel alone. NF-κB DNA-binding activity and the binding ability of NF-κB to the MDR1 promoter were also enhanced in the cells cultured with paclitaxel alone compared to the control cells. However, the expression and activity of NF-κB were significantly decreased in the paclitaxel-TET combination-treated group as compared with the cells treated with paclitaxel alone. On the whole, our findings suggest that TET prevents paclitaxel-induced MDR by inhibiting Pgp overexpression through a mechanism that may involve the inhibition of NF-κB signaling in osteosarcoma.
authors.affiliation: Department of Orthopaedic Traumatology, Tianjin Hospital, Hexi, Tianjin 300211, P.R. China.
authors.forename: Yandong
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Orthopaedic Traumatology, Tianjin Hospital, Hexi, Tianjin 300211, P.R. China.
authors.forename: Fangguo
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Jixian People's Hospital, Jixian, Tianjin 301900, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Orthopaedic Traumatology, Tianjin Hospital, Hexi, Tianjin 300211, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D044182:Benzylisoquinolines / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D044182:Benzylisoquinolines; D016328:NF-kappa B; D009363:Neoplasm Proteins; C009438:tetrandrine; D017239:Paclitaxel