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Archive > Volume 30 Issue 9 > 2023,30(9):789-796. DOI:10.3872/j.issn.1007-385X.2023.09.007 Prev Next
Basic Research
Lycopene inhibits proliferation and promotes apoptosis of renal cancer 786-O cells through the SIRT1/NF-κB axis
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Abstract:
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.
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