目的：探讨番茄红素通过沉默信息调节因子1（SIRT1）/核因子-κB（NF-κB）轴对肾癌786-O 细胞增殖、凋亡的影响。方法：常规培养人正常肾细胞HK-2和人肾癌细胞786-O ，实验分为对照组（0.1% DMSO）、顺铂组（40 μg/mL）、番茄红素低质量浓度（2.5 μg/mL）组、番茄红素高质量浓度（5 μg/mL）组、番茄红素（5 μg/mL）+EX527（SIRT1抑制剂）（3 μmol/L）组。CCK-8法、克隆形成实验检测各组HK-2、786-O 细胞的增殖能力，流式细胞术检测各组786-O 细胞的凋亡，RH123、DCFH-DA 染色分别检测各组786-O 细胞的线粒体膜电位（MMP）、活性氧（ROS）水平，WB法检测各组786-O细胞中凋亡相关蛋白 BAX、Bcl-2、C-casp3和SIRT1/NF-κB轴相关蛋白 SIRT1、p-NF- κB 蛋白的表达。786-O 细胞移植瘤实验检测番茄红素低（5 mg/kg）、高质量浓度（20 mg/Kg）、顺铂（2 mg/kg）、番茄红素（20 mg/kg）+EX527（10 mg/kg）对移植瘤生长的影响，TUNEL法检测各组移植瘤组织中的细胞凋亡。结果：番茄红素呈剂量依赖性地抑制786-O细胞的增殖活性，番茄红素、顺铂均明显抑制786-O细胞的克隆形成能力且促进其凋亡，细胞中MMP损伤率升高而ROS 水平降低，凋亡相关蛋白BAX、C-casp3 表达均显著升高（均P<0.05）而Bcl-2表达下调（P<0.05），SIRT1表达显著升高（P<0.05）而p-NF-κB的表达显著降低（P<0.05），上述作用均可被EX527 逆转；番茄红素、顺铂抑制786-O细胞移植瘤的生长且促进其细胞凋亡，其作用也能被EX527 逆转。结论：番茄红素通过上调SIRT1、抑制NF-κB通路的激活进而抑制786-O细胞增殖且诱导其凋亡。

Objective: To investigate the effects of lycopene on the proliferation and apoptosis of renal carcinoma 786-O cells through silent information regulator 1 (SIRT1)/nuclear factor-kappa B (NF-κB) axis. Methods: Normal human kidney HK-2 cells and human renal cancer 786-O cells were conventionally cultured. The experiment included control group (0.1% DMSO), cisplatin group (40 μg/mL), lycopene low concentration (2.5 μ g/mL) group, lycopene high concentration (5 μ g/mL) group, and lycopene high concentration (5 μg/mL)+ EX527 (SIRT1 inhibitor) (3 μmol/L) group. The proliferation capacity of 786-O cells in each treatment group was detected by CCK-8 method and clonal formation assay. The apoptosis of HK-2 and 786-O cells in each treatment group was detected by flow cytometry. The changes of mitochondrial membrane potential and reactive oxygen species (ROS) in 786-O cells in each treatment group were detected by RH123 and DCFH-DA staining, respectively. The expression of apoptosis-related proteins, BAX, Bcl-2, C-casp3 and SIRT1/NF-κB axis-related proteins SIRT1 and p-NF-Κb, in 786-O cells were detected by WB method. The effects of low concentration lycopene (5 mg/kg), high concentration lycopene (20 mg/Kg), cisplatin (2 mg/kg), and lycopene (20 mg/kg) +EX527 (10 mg/kg) on the growth of 786-O cell transplanted tumor were observed. TUNEL method was used to detect the apoptosis in the tissues of transplanted tumors in each group. Results: Lycopene inhibited the proliferation activity of 786-O cells in a dose dependent manner. Lycopene and cisplatin significantly inhibited the clonogenesis ability of 786-O cells and promoted their apoptosis; moreover, after lycopene and cisplatin treatment, the MMP level was increased while ROS level was decreased, the expression of apoptosis-related proteins BAX and C-casp3 were significantly increased (all P<0.05), while the expression of Bcl-2 was down-regulated (P<0.05), the expression of SIRT1 was significantly increased (all P<0.05) and the expression of p-NF-κB was significantly decreased (all P<0.05). These effects could be reversed by EX527. Lycopene and cisplatin inhibited the growth of 786-O cell grafts in vivo and promoted the apoptosis of tumor cells,and their effects could also be reversed by EX527. Conclusion: Lycopene may inhibit the activation of NF-κB pathway through up-regulation of SIRT1, thus inhibiting proliferation of 786-O cells and inducing apoptosis.

济宁医学院教师科研项目（No. JYFC2018FKJ053）