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.
[1] 郭巍,张秋雨,刘明清,等.银杏叶提取物对甲状腺癌细胞增殖和凋亡的影响[J].现代食品科技,2019,35(8):21-26. [2] 张文婧,苑莉莉,王佳贺.甲状腺癌上皮间质转化机制与中药治疗的研究进展[J].实用药物与临床,2020,23(12):1140-1143. [3] Erdogan S,Doganlar O,Doganlar ZB,et al.Naringin sensitizes human prostate cancer cells to paclitaxel therapy[J].Prostate Int,2018,6(4):126-135. [4] Cano-Gonzalez A,Mauro-Lizcano M,Iglesias-Serret D,et al.Involvement of both caspase-8 and Noxa-activated pathways in endoplasmic reticulum stress-induced apoptosis in triple-negative breast tumor cells[J].Cell Death Dis,2018,9(2):134-149. [5] Lin YW,Chen TY,Hung CY,et al.Melatonin protects brain against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress[J].Int Mol Med,2018,42(1):182-192. [6] Prete A,Borges de Souza P,Censi S,et al.Update on fundamental mechanisms of thyroid cancer[J].Front Endocrinol (Lausanne),2020,11(1):102-111. [7] Ito Y,Miyauchi A,Kihara M,et al.Overall survival of papillary thyroid carcinoma patients:a single-institution long-term follow-up of 5897 patients[J].World Surg,2018,42(3):615-622. [8] 旷历琼,王娜.柚皮苷通过调控ARHI基因表达对结肠癌细胞增殖、凋亡的影响[J].胃肠病学和肝病学杂志,2020,29(7):756-761. [9] Cheng H,Jiang X,Zhang Q,et al.Naringin inhibits colorectal cancer cell growth by repressing the PI3K/AKT/mTOR signaling pathway[J].Exp Ther Med,2020,19(6):3798-3804. [10] Zhu H,Zou X,Lin S,et al.Effects of naringin on reversing cisplatin resistance and the Wnt/β-catenin pathway in human ovarian cancer SKOV3/CDDP cells[J].Int Med Res,2020,48(10):1-9. [11] Tsai TC,Lai KH,Su JH,et al.7-acetylsinumaximol b induces apoptosis and autophagy in human gastric carcinoma cells through mitochondria dysfunction and activation of the PERK/eIF2α/ATF4/CHOP signaling pathway[J].Mar Drugs,2018,16(4):104-116. [12] Fan CL,Yao ZH,Ye MN,et al.Fuziline alleviates isoproterenol-induced myocardial injury by inhibiting ROS-triggered endoplasmic reticulum stress via PERK/eIF2α/ATF4/Chop pathway[J].Cell Mol Med,2020,24(2):1332-1344. [13] Albayrak D,Doganlar O,Erdogan S,et al.Naringin combined with NF-κB inhibition and endoplasmic reticulum stress induces apoptotic cell death via oxidative stress and the PERK/eIF2α/ATF4/CHOP axis in HT29 colon cancer cells[J].Biochem Genet,2021,59(1):159-184.
2022, Vol. 28 
冀公网安备13080202000677号