New Approach for Treatment of Primary Liver Tumors: The Role of Quercetin
New Approach for Treatment of Primary Liver Tumors: The Role of Quercetin
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DOI：
10.1080/01635581.2016.1145245
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发表时间：
2016-02-17
影响因子：
2.9
通讯作者：
Botelho, Maria Filomena
中科院分区：
文献类型：
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作者：
Brito, Ana Filipa;Ribeiro, Marina;Botelho, Maria Filomena
肝细胞癌（HCC）是最常见的原发性肝脏肿瘤（PLT），胆管癌（CC）是第二常见的。 PLT 中葡萄糖转运蛋白 1 (GLUT-1) 的表达增加，因此建议将其作为治疗靶点。类黄酮与槲皮素一样，是 GLUT-1 竞争性抑制剂，可被视为 PLT 的潜在治疗剂。本研究的目的是评估槲皮素在三种人 HCC 细胞系（HepG2、HuH7 和 Hep3B2.1-7）和人 CC 细胞系 (TFK-1) 中的抗癌活性。还评估了槲皮素和索拉非尼（一种在临床实践中用于晚期 HCC 患者的非特异性多激酶抑制剂）之间可能的协同作用。结果发现，在所有细胞系中，槲皮素均诱导代谢活性抑制和细胞凋亡导致的细胞死亡，随后BAX/BCL-2比值增加。槲皮素处理导致 HepG2、Hep3B2.1-7 和 TFK-1 细胞系 DNA 损伤。槲皮素的作用似乎与 P53 无关。与槲皮素一起孵育可诱导 GLUT-1 膜表达增加，随后细胞质部分减少，观察到 F-18-FDG 摄取减少，表明 GLUT-1 竞争性抑制。当索拉非尼和槲皮素同时添加至 HCC 细胞系时，注意到协同作用的发生。因此，使用槲皮素似乎是通过 GLUT-1 竞争性抑制来治疗 PLT 的一种有前途的方法。
Hepatocellular carcinoma (HCC) is the most common primary liver tumor (PLT), with cholangiocarcinoma (CC) being the second most frequent. Glucose transporter 1 (GLUT-1) expression is increased in PLTs and therefore it is suggested as a therapeutic target. Flavonoids, like quercetin, are GLUT-1 competitive inhibitors and may be considered as potential therapeutic agents for PLTs. The objective of this study was evaluation of quercetin anticancer activity in three human HCC cell lines (HepG2, HuH7, and Hep3B2.1-7) and in a human CC cell line (TFK-1). The possible synergistic effect between quercetin and sorafenib, a nonspecific multikinase inhibitor used in clinical practice in patients with advanced HCC, was also evaluated. It was found that in all the cell lines, quercetin induced inhibition of the metabolic activity and cell death by apoptosis, followed by increase in BAX/BCL-2 ratio. Treatment with quercetin caused DNA damage in HepG2, Hep3B2.1-7, and TFK-1 cell lines. The effect of quercetin appears to be independent of P53. Incubation with quercetin induced an increase in GLUT-1 membrane expression and a consequent reduction in the cytoplasmic fraction, observed as a decrease in F-18-FDG uptake, indicating a GLUT-1 competitive inhibition. The occurrence of synergy when sorafenib and quercetin were added simultaneously to HCC cell lines was noticed. Thus, the use of quercetin seems to be a promising approach for PLTs through GLUT-1 competitive inhibition.