Hirata M, Kusuzaki K, Takeshita H, Hashiguchi S, Hirasawa Y, Ashihara T
Department of Orthopaedic Surgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan.
Anticancer Res. 2001 Jan-Feb;21(1A):317-20.
Multidrug resistance (MDR) is one of the major problems in osteosarcoma chemotherapy. Therefore, methods of overcoming MDR are urgently needed. In this study, we investigated the effects of pulsing electromagnetic field stimulation (PEMFs) on a MDR murine osteosarcoma cell line which strongly expresses P-glycoprotein (P-gp). To assess the reversal effects of PEMFs on doxorubicin (DOX) resistance, MTT assay was applied. Viable cells were assessed by the trypan blue exclusion test. Fluorescence intensity of DOX binding to nuclear DNA of each cell was measured using a cytofluorometer. Changes in P-gp expression in each cell were detected by the indirect immunofluorescence method using an antibody to Pgp. PEMFs increased DOX binding ability to nuclear DNA and inhibited cell growth, although it had no significant effect on P-gp expression. These findings indicated that PEMFs reversed the DOX resistance of the MOS/ADR1 cells by inhibiting P-gp function. The results suggested that PEMFs may be useful as a local treatment for MDR osteosarcoma.
多药耐药性(MDR)是骨肉瘤化疗中的主要问题之一。因此,迫切需要克服MDR的方法。在本研究中,我们研究了脉冲电磁场刺激(PEMFs)对一种强烈表达P-糖蛋白(P-gp)的MDR小鼠骨肉瘤细胞系的影响。为了评估PEMFs对阿霉素(DOX)耐药性的逆转作用,采用了MTT法。通过台盼蓝排斥试验评估活细胞。使用细胞荧光计测量DOX与每个细胞核DNA结合的荧光强度。使用抗Pgp抗体通过间接免疫荧光法检测每个细胞中P-gp表达的变化。PEMFs增加了DOX与核DNA的结合能力并抑制了细胞生长,尽管它对P-gp表达没有显著影响。这些发现表明,PEMFs通过抑制P-gp功能逆转了MOS/ADR1细胞的DOX耐药性。结果表明,PEMFs可能作为MDR骨肉瘤的局部治疗方法有用。