Fucoxanthin and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Synergistically Promotes Apoptosis of Human Cervical Cancer Cells by Targeting PI3K/Akt/NF-κB Signaling Pathway.
Fucoxanthin and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Synergistically Promotes Apoptosis of Human Cervical Cancer Cells by Targeting PI3K/Akt/NF-κB Signaling Pathway.
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DOI：
10.12659/msm.905360
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发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Zheng J
中科院分区：
文献类型：
--
作者：
Jin Y;Qiu S;Shao N;Zheng J
岩藻黄质是一种存在于棕色海藻叶绿体中的类胡萝卜素。肿瘤坏死因子相关凋亡诱导配体（TRAIL）是一种细胞因子，可选择性诱导许多肿瘤细胞凋亡，是抗肿瘤治疗的有吸引力的候选者。用岩藻黄质或 TRAIL 处理人宫颈癌细胞系 HeLa、SiHa 和 CaSki 后。通过2,3-双(2-甲氧基-4-硝基-5-磺基苯基)-2-四唑鎓5-甲酰苯胺(XTT)法测定细胞活力。通过流式细胞术（FCM）测量细胞凋亡。磷脂酰肌醇 3 激酶 (PI3K)、蛋白激酶 B (Akt)、磷酸化 Akt (p-Akt)、NF-κB 核因子 k 基因结合 (NF-κB) 的蛋白质表达。通过蛋白质印迹分析测量 B 细胞抑制剂 α 中 kappa 轻链多肽基因增强子的磷酸化核因子 (p-IκBa)。通过 RNA 制备和定量逆转录聚合酶链反应 (RT-PCR) 测量 Bax 和 Bcl2 的 mRNA 表达。本研究中，在细胞凋亡方面的有效性依次为：TRAIL加岩藻黄质>岩藻黄质>TRAIL，说明岩藻黄质与TRAIL联合对人宫颈癌细胞的凋亡产生了较强的协同作用。此外，我们发现上游信号 PI3K/Akt 和 NF-κB 通路介导的细胞凋亡被 TRAIL 激活，并被岩藻黄质抑制。通过使用PI3K和NF-κB抑制剂LY49002和PDTC，我们发现岩藻黄质或TRAIL诱导的人宫颈癌细胞凋亡明显下调。综上所述，这些发现表明岩藻黄质和 TRAIL 通过靶向 PI3K/Akt/NF-κB 信号通路增加人宫颈癌细胞的凋亡。
Fucoxanthin is a carotenoid present in the chloroplasts of brown seaweeds. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively induces apoptosis in many tumor cells and is an attractive candidate for antitumor therapies. After human cervical cancer cell lines HeLa, SiHa, and CaSki were treated with fucoxanthin or TRAIL. Cell viability was determined by 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2-tetrazolium 5-carboxanilide (XTT) method. Apoptosis was measured by flow cytometry (FCM). Protein expression of phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt), phosphated Akt (p-Akt), NF-κB nuclear factor-k-gene binding (NF-κB). Phosphated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (p-IκBa), was measured by Western blot analysis. mRNA expression of Bax and Bcl2 was measured by RNA preparation and quantitative reverse transcription polymerase chain reaction (RT-PCR). In the present study, the effectiveness in terms of apoptosis was as follows: TRAIL plus fucoxanthin>fucoxanthin>TRAIL, indicating the combination of fucoxanthin and TRAIL, produced a strong synergistic effect on apoptosis in human cervical cancer cells. Additionally, we found that upstream signaling PI3K/Akt and NF-κB pathways-mediated cell apoptosis was activated by TRAIL and suppressed by fucoxanthin. By using PI3K and NF-κB inhibitors LY49002 and PDTC, we found that fucoxanthin- or TRAIL-induced apoptosis of human cervical cancer cells was obviously down-regulated. Taken together, these findings suggest that fucoxanthin and TRAIL increased the apoptosis in human cervical cancer cells by targeting the PI3K/Akt/NF-κB signaling pathway.
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