Fenofibrate attenuates the cytotoxic effect of cisplatin on lung cancer cells by enhancing the antioxidant defense system in vitro.
Fenofibrate attenuates the cytotoxic effect of cisplatin on lung cancer cells by enhancing the antioxidant defense system in vitro.
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DOI：
10.3892/ol.2023.13899
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发表时间：
2023-07
期刊：
影响因子：
2.9
通讯作者：
Aoshiba K
中科院分区：
文献类型：
--
作者：
Kogami M;Abe S;Nakamura H;Aoshiba K
非诺贝特（FF）是一种过氧化物酶体增殖物激活受体(PPAR) α激动剂，广泛用于治疗高脂血症。除降血脂作用外，它还具有多效性。研究表明，当使用FF的浓度高于临床相关浓度时，FF会对某些癌细胞产生细胞毒性作用；另一方面，其对正常细胞的保护作用也有报道。本研究在体外评估了FF对顺铂（CDDP）肺癌细胞毒性的影响。结果表明，FF对肺癌细胞的作用取决于其浓度。FF≤50µM（临床可达到的血药浓度）可减弱CDDP对肺癌细胞的细胞毒性，而FF≥100µM（虽然临床无法达到）具有抗癌作用。FF抑制CDDP细胞毒性的机制涉及PPAR-α-依赖性芳烃受体（AhR）的表达，进而刺激核因子红系2相关因子2 （Nrf2）的表达和抗氧化剂的产生，从而保护肺癌细胞免受CDDP引起的氧化损伤。综上所述，本研究揭示，在临床相关浓度下，FF通过激活PPAR-α-PPAR反应元件- ahr外源反应元件- nrf2 -抗氧化反应元件的通路，增强抗氧化防御系统，从而减弱CDDP对肺癌细胞的细胞毒性。这些发现表明，FF与CDDP同时使用可能会损害化疗的疗效。虽然FF的抗癌特性最近引起了人们的广泛关注，但其浓度必须超过临床相关浓度。
Fenofibrate (FF) is a peroxisome proliferator- activated receptor (PPAR)-α agonist that is widely used for the treatment of hyperlipidemia. It has been shown to have pleiotropic actions beyond its hypolipidemic effect. FF has been shown to exert a cytotoxic effect on some cancer cells when used at higher than clinically relevant concentrations; on the other hand, its cytoprotective effect on normal cells has also been reported. The present study assessed the effect of FF on cisplatin (CDDP) cytotoxicity to lung cancer cells in vitro. The results demonstrated that the effect of FF on lung cancer cells depends on its concentration. FF at ≤50 µM, which is a clinically achievable blood concentration, attenuated CDDP cytotoxicity to lung cancer cells, whereas FF at ≥100 µM, albeit clinically unachievable, had an anticancer effect. The mechanism of FF attenuation of CDDP cytotoxicity involved PPAR-α-dependent aryl hydrocarbon receptor (AhR) expression, which in turn stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and antioxidant production, resulting in lung cancer cell protection from CDDP-evoked oxidative damage. In conclusion, the present study revealed that FF, at clinically relevant concentrations, attenuated CDDP cytotoxicity to lung cancer cells by enhancing the antioxidant defense system through activation of a pathway that involves the PPAR-α-PPAR response element-AhR xenobiotic response element-Nrf2-antioxidant response element. These findings suggested that concomitant use of FF with CDDP may compromise the efficacy of chemotherapy. Although the anticancer property of FF has recently attracted much attention, concentrations that exceed clinically relevant concentrations are required.
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影响因子：
5.6
作者：
Davies SP;Mycroft-West CJ;Pagani I;Hill HJ;Chen YH;Karlsson R;Bagdonaite I;Guimond SE;Stamataki Z;De Lima MA;Turnbull JE;Yang Z;Vicenzi E;Skidmore MA;Khanim FL;Richardson A
通讯作者：
Richardson A
影响因子：
2.9
作者：
Cortes-Lopez F;Sanchez-Mendoza A;Centurion D;Cervantes-Perez LG;Castrejon-Tellez V;Del Valle-Mondragon L;Soria-Castro E;Ramirez V;Sanchez-Lopez A;Pastelin-Hernandez G;Garcia-Niño WR;Sanchez-Aguilar M;Ibarra-Lara L
通讯作者：
Ibarra-Lara L
DOI：
10.3390/molecules22010031
发表时间：
2016-12-28
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Ibarra-Lara L;Sánchez-Aguilar M;Sánchez-Mendoza A;Del Valle-Mondragón L;Soria-Castro E;Carreón-Torres E;Díaz-Díaz E;Vázquez-Meza H;Guarner-Lans V;Rubio-Ruiz ME
通讯作者：
Rubio-Ruiz ME
影响因子：
6.4
作者：
Berndtsson, Maria;Hagg, Maria;Linder, Stig
通讯作者：
Linder, Stig
影响因子：
5.3
作者：
Desager, JP;Horsmans, Y;Harvengt, C
通讯作者：
Harvengt, C