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目的分析可诱导一氧化氮合酶(iNOS)对乳腺癌细胞化学敏感性的影响,评价新型蒽醌类生物还原化合物RH1对乳腺癌细胞毒性和乏氧选择性。方法实验以人乳腺癌细胞MDA-MB-231wt和其转染空载体的对照组细胞(PEF-vector)及一氧化氮合酶基因转染的细胞克隆(i NOS10)为实验对象。噻唑蓝(MTT)法比较不同酶活性的细胞克隆对顺铂等抗肿瘤药物和丝裂霉素C(MMC)衍生物-2,5-二氮丙啶-6-羟甲基-3-甲基苯-1,4-二酮(RH1)的敏感性的差异。结果同对照组细胞相比,i NOS10细胞对顺铂等几种抗肿瘤药物呈现不同程度的耐受,而对阿霉素的敏感性有所增强(P<0.05),用L-甲基盐酸精氨酸抑制细胞中NO的合成,则会降低i N-OS10细胞对阿霉素的敏感性,而对其他几种抗肿瘤药物的敏感性无显著影响;生物还原化合物RH1是高毒性的化合物,IC50较MMC下降577倍;乏氧条件下,细胞对RH1的化学敏感性显著增强,流式细胞术显示RH1可以引起i NOS10细胞周期的G2/M阻滞。结论MMC衍生物RH1是高细胞毒性的化合物,可诱导一氧化氮合酶活性的增强,也可引起肿瘤细胞对部分抗肿瘤药物的敏感性降低,且对高表达i NOS的细胞具有乏氧选择性的损伤作用。
Objective To analyze the effect of inducible nitric oxide synthase (iNOS) on the chemosensitivity of breast cancer cells, and to evaluate the cytotoxicity and hypoxia selectivity of the novel terpenoid bioreductive compound RH1 for breast cancer. Methods Human breast cancer cells MDA-MB-231wt and its transfected control vector (PEF-vector) and iNOS 10 gene transfected cell clone (i NOS10) were used as experimental subjects. The MTT assay compares cell clones with different enzyme activities to antitumor agents such as cisplatin and mitomycin C (MMC) derivatives-2,5-diazimine-6-hydroxymethyl-3-methyl The difference in the sensitivity of phenylbenzene-1,4-dione (RH1). Results Compared with control cells, iNOS10 cells showed varying degrees of tolerance to several antitumor drugs such as cisplatin, while the sensitivity to doxorubicin was enhanced (P<0.05). Arginine inhibited the synthesis of NO in cells and decreased the sensitivity of iN-OS10 cells to adriamycin, but had no significant effect on the sensitivity of several other antitumor drugs. Bioreductive compound RH1 is a highly toxic compound. The IC50 was 577-fold lower than that of MMC. Under hypoxic conditions, the cell’s chemosensitivity to RH1 was significantly enhanced. Flow cytometry showed that RH1 could induce G2/M arrest of the iNOS10 cell cycle. Conclusion RH1, an MMC derivative, is a highly cytotoxic compound that induces an increase in the activity of nitric oxide synthase. It also causes a decrease in the sensitivity of tumor cells to some antitumor drugs and has a hypoxic option for cells that express high iNOS. Sexual damage effects.