柚皮苷调节PERK/eIF2α/ATF4/CHOP轴对甲状腺癌细胞增殖凋亡迁移侵袭的影响

doi:10.3969/j.issn.1006-6233.2022.08.07

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Abstract Objective: To analyze the effects of naringin on the proliferation, apoptosis, migration and invasion of thyroid cancer cells B-CPAP by regulating protein kinase R-like ER kinase/eukaryotic translation initiation factor alpha 2/activating transcription factor 4/CCAAT/ enhancer-binding protein homologous protein (PERK/eIF2α/ATF4/CHOP) axis. Methods: B-CPAP cells were treated with 1, 5, 10, 20 μmol/L naringin, B-CPAP cells treated with 5 μmol/L PERK inhibitor GSK2606414+20 μmol/L naringin were used as the inhibitor group, and B-CPAP cells without naringin as control group. MTT method was used to detect the proliferation of B-CPAP cells in each group; flow cytometry was used to detect apoptosis of B-CPAP cells in each group; cell scratch test was used to detect the migration of B-CPAP cells in each group; Transwell experiment was used to detect the invasion of B-CPAP cells in each group; and Western blot method was used to detect the expression levels of PERK/eIF2α/ATF4/CHOP axis-related proteins, Vimentin, E-cadherin, N-cadherin, Bcl-2 related X protein(Bax), B-cell lymphoma-2(Bcl-2) in B-CPAP cells of each group. Results: Compared with the control group, the proliferation rate of B-CPAP cells [(100.00±0.00)% vs. (90.73±5.25)%, (76.52±3.19)%, (62.84±3.25)%, (48.39±2.14)%] decreased sequentially after treatment with 1, 5, 10, and 20 μmol/L naringin for 48, in a concentration-dependent manner (P<0.05); after treatment with 20 μmol/L naringin for 12 h, 24 h, and 48 h, the proliferation rate of B-CPAP cells decreased sequentially[(82.37±3.06)% vs. (71.45±2.73)% vs. (48.39±2.14)%], in a time-dependent manner (P<0.05). Compared with the control group, the apoptosis rate of B-CPAP cells [(6.37±0.44)% vs. (9.46±0.83)%, (18.59±2.16)%, (33.41±4.29)%, (50.76±5.17)%] increased with naringin concentration increasing (1, 5, 10, 20 μmol/L), the wound healing rate[(62.74±2.86)% vs. (55.26±2.49)%, (46.38±2.17)%, (39.15±1.84)%, (33.42±1.39)%] and the number of transmembrane cells of B-CPAP cells[(70.54±6.12) vs. (57.78±5.62), (42.59±4.86), (29.27±3.91), (65.62±5.83)] decreased, the levels of p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, E-cadherin and Bax proteins in B-CPAP cells gradually increased, the levels of Vimentin, N-cadherin and Bcl-2 proteins in B-CPAP cells gradually reduced, in a concentration-dependent manner (P<0.05). The B-CPAP cell proliferation rate[(94.16±5.38)% vs. (48.39±2.14)%], scratch healing rate[(58.65±2.73)% vs. (33.42±1.39)%], and number of penetrating cells[(65.62±5.83)% vs. (16.49±3.04)%] in the inhibitor group were higher than those in the 20 μmol/L group (P<0.05), the apoptosis rate[(7.82±0.65)% vs. (50.76±5.17)%] and levels of p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, E-cadherin and Bax proteins were lower than those in the 20 μmol/L group, the levels of Vimentin, N-cadherin and Bcl-2 proteins were higher than those in the 20 μmol/L group (P<0.05). Conclusion: Naringin can inhibit the proliferation of B-CPAP cells, promote their apoptosis, and reduce the migration and invasion abilities of B-CPAP cells by activating the PERK/eIF2α/ATF4/CHOP axis.

Key words： Naringin Thyroid cancer Migration Invasion

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2022.08.07 OR http://www.hbyxzzs.cn/EN/Y2022/V28/I8/1268

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