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目的探讨舒尼替尼对吉非替尼耐药的肺癌细胞的治疗作用及意义。方法四甲基偶氮唑蓝(MTT)法检测舒尼替尼对28例肺癌患者肿瘤组织提取的吉非替尼耐药细胞的增殖抑制作用;Cell Titer-Glo法检测舒尼替尼给药后,耐药细胞株对吉非替尼的敏感性;流式细胞术方法检测舒尼替尼作用后吉非替尼耐药细胞中Rh-123的含量;Western blot法检测舒尼替尼给药后吉非替尼耐药细胞中多药耐药蛋白(MDR)、核转录因子κB(NF-κB)及血管内皮生长因子(VEGF)蛋白的表达情况。结果舒尼替尼剂量依赖性的抑制吉非替尼耐药细胞的增殖,IC_(50)值为(6.73±1.57)μmol·L~(-1);舒尼替尼可显著增加耐药细胞对吉非替尼的敏感性,降低吉非替尼抑制耐药细胞增殖的IC_(50)值,1和2μmol·L~(-1)舒尼替尼作用耐药细胞株的吉非替尼IC50值分别为(38.64±1.29)与(20.37±1.75)μmol·L~(-1)。1μmol·L~(-1)舒尼替尼给药后可显著增加耐药细胞中Rh-123的含量(P<0.05),荧光密度是对照组的2.44倍;2μmol·L~(-1)舒尼替尼给药后耐药细胞中Rh-123的含量与对照组相比具有显著性差异(P<0.01),荧光密度是对照组的5.64倍;1和2μmol·L~(-1)的舒尼替尼给药后可显著减少吉非替尼耐药细胞中MDR、NF-κB及VEGF蛋白的表达,并具有剂量依赖性。结论舒尼替尼可逆转吉非替尼耐药,为临床治疗吉非替尼耐药的患者提供理论依据。
Objective To investigate the therapeutic effect and significance of sunitinib on gefitinib-resistant lung cancer cells. Methods MTT assay was used to detect the inhibitory effect of sunitinib on the proliferation of gefitinib-resistant cells extracted from tumor tissues of 28 patients with lung cancer. Cell Titer-Glo assay was used to determine the effect of sunitinib administration The sensitivity of gefitinib to drug resistant cell lines was detected by flow cytometry. The Rh-123 content in gefitinib-resistant cells was detected by flow cytometry. Sunitinib The expression of multidrug resistance protein (MDR), nuclear factor kappa B (NF-κB) and vascular endothelial growth factor (VEGF) protein in gefitinib-resistant cells were determined by MTT assay. Results Sunitinib inhibited the proliferation of gefitinib-resistant cells in a dose-dependent manner with an IC 50 value of (6.73 ± 1.57) μmol·L -1. Sunitinib significantly increased the number of resistant cells Sensitivity to gefitinib and gefitinib inhibited the proliferation of drug-resistant cells IC 50, 1 and 2 μmol·L -1 Sunitinib-resistant cell lines with gefitinib IC50 values were (38.64 ± 1.29) and (20.37 ± 1.75) μmol·L -1, respectively. After treatment with 1 μmol·L -1 sunitinib, the Rh-123 content in drug-resistant cells was significantly increased (P <0.05), and the fluorescence intensity was 2.44 times that of the control group. The concentration of 2 μmol·L -1 The concentration of Rh-123 in drug-resistant cells after sunitinib administration was significantly different from that in control group (P <0.01), and the fluorescence intensity was 5.64 times higher than that in control group. The levels of Rh-123 in 1 and 2 μmol·L -1 Sunitinib could significantly reduce the expression of MDR, NF-κB and VEGF in gefitinib-resistant cells in a dose-dependent manner. Conclusion Sunitinib can reverse gefitinib resistance and provide theoretical basis for clinical treatment of gefitinib-resistant patients.