期刊
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
卷 39, 期 4, 页码 993-1000出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2017.2895
关键词
osteosarcoma; tetrandrine; multidrug resistance; P-glycoprotein; nuclear factor-B signaling pathway
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)-B, and the expression levels of NF-B and p-IB- were all enhanced in the cells cultured with paclitaxel alone. NF-B DNA-binding activity and the binding ability of NF-B 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-B 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-B signaling in osteosarcoma.
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