Anti-tumor Effect of Oleic Acid in Hepatocellular Carcinoma Cell Lines via Autophagy Reduction.
Anti-tumor Effect of Oleic Acid in Hepatocellular Carcinoma Cell Lines via Autophagy Reduction.
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DOI：
10.3389/fcell.2021.629182
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发表时间：
2021
影响因子：
5.5
通讯作者：
Giampietri C
中科院分区：
文献类型：
--
作者：
Giulitti F;Petrungaro S;Mandatori S;Tomaipitinca L;de Franchis V;D'Amore A;Filippini A;Gaudio E;Ziparo E;Giampietri C
油酸是橄榄油的一种成分。众所周知，橄榄油对健康有益，例如预防肝脏脂肪变性和某些癌症类型。在本研究中，我们重点研究了OA在肝细胞癌中的作用，研究了肝癌细胞系(Hep3B和Huh7.5)和健康人肝源性细胞系(THLE-2)对OA处理(50-300μM)的反应。与健康细胞相比，给予OA后，肝癌细胞中的脂质积累增加，Perilipin-2增加，自噬减少。经Alamar Blue染色检测，10%胎牛血清白蛋白可显著降低300μM肝癌细胞系的存活率，并呈剂量依赖性地降低细胞周期蛋白D1的表达，而对健康肝细胞则无效。此外，在300μM剂量下，OA使细胞死亡增加约30%，诱导肝癌细胞凋亡和坏死，但对健康肝细胞无影响。此外，OA还可诱导Hep3B细胞衰老，降低两种肝癌细胞系中P-ERK的表达，并显著抑制肝癌细胞中抗凋亡蛋白c-Flip和Bcl2的表达，但对正常肝细胞无明显影响。所有这些结果使我们得出结论，在OA处理后，这两种肝癌细胞系发生了不同的细胞死亡过程。此外，300μ-MOA可显著降低两种肝癌细胞系的迁移和侵袭能力，而对健康细胞无明显影响。最后，我们使用自噬诱导剂Torin-1研究了自噬在OA依赖效应中的作用。与单一的OA治疗相比，联合的OA/Torin-1治疗减少了脂质堆积和细胞死亡。因此，我们得出结论，在肝癌细胞系中，OA的作用至少部分依赖于OA诱导的自噬减少。综上所述，我们首次报道了人肝细胞癌细胞系中依赖自噬的相关抗癌作用。
Oleic acid (OA) is a component of the olive oil. Beneficial health effects of olive oil are well-known, such as protection against liver steatosis and against some cancer types. In the present study, we focused on OA effects in hepatocellular carcinoma (HCC), investigating responses to OA treatment (50–300 μM) in HCC cell lines (Hep3B and Huh7.5) and in a healthy liver-derived human cell line (THLE-2). Upon OA administration higher lipid accumulation, perilipin-2 increase, and autophagy reduction were observed in HCC cells as compared to healthy cells. OA in the presence of 10% FBS significantly reduced viability of HCC cell lines at 300 μM through Alamar Blue staining evaluation, and reduced cyclin D1 expression in a dose-dependent manner while it was ineffective on healthy hepatocytes. Furthermore, OA increased cell death by about 30%, inducing apoptosis and necrosis in HCC cells but not in healthy hepatocytes at 300 μM dosage. Moreover, OA induced senescence in Hep3B, reduced P-ERK in both HCC cell lines and significantly inhibited the antiapoptotic proteins c-Flip and Bcl-2 in HCC cells but not in healthy hepatocytes. All these results led us to conclude that different cell death processes occur in these two HCC cell lines upon OA treatment. Furthermore, 300 μM OA significantly reduced the migration and invasion of both HCC cell lines, while it has no effects on healthy cells. Finally, we investigated autophagy role in OA-dependent effects by using the autophagy inducer torin-1. Combined OA/torin-1 treatment reduced lipid accumulation and cell death as compared to single OA treatment. We therefore concluded that OA effects in HCC cells lines are, at least, in part dependent on OA-induced autophagy reduction. In conclusion, we report for the first time an autophagy dependent relevant anti-cancer effect of OA in human hepatocellular carcinoma cell lines.
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影响因子：
2.4
作者：
Lim DW;Jeon H;Kim M;Yoon M;Jung J;Kwon S;Cho S;Um MY
通讯作者：
Um MY
DOI：
10.1016/j.bbrc.2018.02.097
发表时间：
2018-10-07
影响因子：
3.1
作者：
Maan M;Peters JM;Dutta M;Patterson AD
通讯作者：
Patterson AD
肝细胞癌中的自噬激活通过活性氧调节促进奥沙利铂的耐受性
影响因子：
11.5
作者：
Ding, Zhen-Bin;Hui, Bo;Fan, Jia
通讯作者：
Fan, Jia
影响因子：
--
作者：
Chava S;Lee C;Aydin Y;Chandra PK;Dash A;Chedid M;Thung SN;Moroz K;Wu T;Nayak NC;Dash S
通讯作者：
Dash S
影响因子：
2.8
作者：
Giampietri, Claudia;Tomaipitinca, Luana;Facchiano, Antonio
通讯作者：
Facchiano, Antonio