Total Flavonoids of Litchi Seed Attenuate Prostate Cancer Progression Via Inhibiting AKT/mTOR and NF-kB Signaling Pathways.
Total Flavonoids of Litchi Seed Attenuate Prostate Cancer Progression Via Inhibiting AKT/mTOR and NF-kB Signaling Pathways.
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Litchi种子的总类黄酮通过抑制AKT/MTOR和NF-KB信号传导途径来减弱前列腺癌的进展。
DOI：
10.3389/fphar.2021.758219
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发表时间：
2021
影响因子：
5.6
通讯作者：
Guo H
中科院分区：
文献类型：
--
作者：
Chang M;Zhu D;Chen Y;Zhang W;Liu X;Li XL;Cheng Z;Su Z;Zhang J;Lu Y;Guo H
荔枝核传统上用于治疗泌尿系统肿瘤，包括前列腺癌（PCa）。然而，荔枝核的有效成分及其对PCa细胞生长和转移的作用机制尚不清楚。本研究探讨荔枝核总黄酮（TFLS）对前列腺癌细胞系PC 3和DU 145的作用及其分子机制。TFLS能显著抑制PCa细胞增殖，诱导细胞凋亡，并抑制细胞迁移和侵袭。此外，我们观察到TFLS上调上皮生物标志物E-cadherin的表达，下调间充质生物标志物波形蛋白。TFLS还可增加PC 3和DU 145细胞中切割PRAP和Bax的表达，降低Bcl-2的表达。TFLS通过降低AKT的磷酸化水平及下游信号转导分子mTOR、IκBα和NF-κ B的活性，抑制AKT信号通路。最后，TFLS处理的小鼠表现出肿瘤大小的显著减小，而在体内主要器官中没有毒性。上述结果提示TFLS可通过抑制AKT/mTOR和NF-κB信号通路，诱导PCa细胞凋亡，逆转EMT表型，从而抑制PCa细胞的体内生长和体外增殖及转移。总之，我们的数据提供了新的见解TFLS作为一种新的有效的抗癌剂治疗前列腺癌的作用。
Litchi seeds have been traditionally used in Chinese herbal formula for urologic neoplasms including prostate cancer (PCa). However, the effective components of Litchi seeds and the mechanisms of their actions on PCa cell growth and metastasis remain unclear. In this study, we investigated the effects and molecular mechanisms of the Total Flavonoid of Litchi Seed (TFLS) in PCa PC3 and DU145 cell lines. We found that TFLS significantly inhibited the PCa cell proliferation, induced apoptosis, and prevented cell migration and invasion. Furthermore, we observed that TFLS upregulated the expression of epithelial biomarker E-cadherin and downregulated mesenchymal biomarker Vimentin. TFLS also increased the expression of cleaved-PRAP and Bax, and decreased the expression of Bcl-2 in both PC3 and DU145 cells. Besides, TFLS inhibited AKT signaling pathway by reducing the phosphorylation of AKT and activities of downstream signal transducers including mTOR, IκBα and NF-kB. Finally, TFLS treated mice exhibited a significant decrease in tumor size without toxicity in major organs in vivo. These results indicated that TFLS could suppress PCa cell growth in vivo and inhibit PCa cell proliferation and metastasis in vitro through induction of apoptosis and phenotypic reversal of EMT, which may be achieved by inhibiting the AKT/mTOR and NF-κB signaling pathways. Taken together, our data provide new insights into the role of TFLS as a novel potent anti-cancer agent for the treatment of PCa.
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DOI：
10.3760/cma.j.issn.1007-3418.2018.07.011
发表时间：
2018-07-20
影响因子：
--
作者：
Qin, G J;Zhao, Y Z;Lu, Q
通讯作者：
Lu, Q
DOI：
10.1016/j.bbrc.2004.04.185
发表时间：
2004-06-25
影响因子：
3.1
作者：
Chandrasekar, B;Marelli-Berg, FM;Murray, DR
通讯作者：
Murray, DR
荔枝籽提取物通过 Akt/GSK-3 beta 信号传导诱导细胞凋亡和减弱 EMT，从而减少前列腺癌的进展
影响因子：
4.6
作者：
Guo H;Luo H;Yuan H;Xia Y;Shu P;Huang X;Lu Y;Liu X;Keller ET;Sun D;Deng J;Zhang J
通讯作者：
Zhang J
影响因子：
--
作者：
Hsu CP;Lin CC;Huang CC;Lin YH;Chou JC;Tsia YT;Su JR;Chung YC
通讯作者：
Chung YC
影响因子：
254.7
作者：
Siegel, Rebecca L.;Miller, Kimberly D.;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin