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荜澄茄酮通过诱导细胞凋亡和抑制 PI3K/AKT/mTOR 信号通路抑制人前列腺癌细胞 PC-3 的增殖。

Zingerone suppresses cell proliferation via inducing cellular apoptosis and inhibition of the PI3K/AKT/mTOR signaling pathway in human prostate cancer PC-3 cells.

机构信息

Department of Urology, Chongqing Hospital of Traditional Chinese Medicine /Chongqing Academy of Traditional Chinese Medicine, Chongqing, China.

Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China.

出版信息

J Biochem Mol Toxicol. 2021 Jan;35(1):e22611. doi: 10.1002/jbt.22611. Epub 2020 Sep 9.

DOI:10.1002/jbt.22611
PMID:32905641
Abstract

Prostate cancer (PCa) is both the foremost and second cause of cancer death in the male population. Patients with hormone-dependent PCa are initially sensitive to androgen-deprivation therapy, later the cancer progress to a hormone-independent state and fails to respond and progress to the metastatic stage, where the cells gain the ability to escape cell death and develop resistance to current therapies, thereby leading to migration, invasion, and metastasis of cancer. Many clinical trials using nutraceuticals on cancer using human subjects have also been extensively studied, these studies confirm the efficacy of drugs tested in in vitro and in vivo preclinical models. Among various dietary phytochemicals, ginger is commonly used in the diet and possesses many active principles that act against cancer. Among various active principles, zingerone is a key active phenolic compound present in Zingiber officinale (Ginger), it has potent antioxidant property and it acts against carcinogens. The present study evaluated the efficacy of zingerone at different doses on the PCa cell line regarding apoptosis, upstream signing molecules such as Akt/mTOR, and migration metastasis. A cell viability assay using MTT was performed to estimate the percentage of viability of zingerone-treated PC-3 cells. The mitochondrial membrane potential, intracellular reactive oxygen species, and apoptosis induction in the zingerone-treated PC-3 cells were studied by using different fluorescence staining techniques. The expression patterns of PI3K, AKT, p-AKT, mTOR, and p-mTOR were investigated through the Western blot analysis assay. Zingerone induces apoptosis and alters Akt/mTOR molecules; it also inhibits cell adhesion and migration of PCa cells. From the present study, it is concluded that zingerone effectively induces apoptosis and inhibits cancer signaling, thereby acting as a potent drug against PCa.

摘要

前列腺癌(PCa)是男性人群中癌症死亡的首要和第二大原因。患有激素依赖性 PCa 的患者最初对雄激素剥夺疗法敏感,随后癌症进展为激素非依赖性状态,无法响应并进展为转移阶段,此时细胞获得逃避细胞死亡并对当前疗法产生耐药性的能力,从而导致癌症的迁移、侵袭和转移。许多使用人类受试者的营养保健品治疗癌症的临床试验也得到了广泛研究,这些研究证实了在体外和体内临床前模型中测试的药物的疗效。在各种膳食植物化学物质中,生姜在饮食中很常见,具有许多对抗癌症的活性成分。在各种活性成分中,姜酮是生姜(Zingiber officinale)中存在的一种关键活性酚类化合物,它具有很强的抗氧化特性,可对抗致癌物质。本研究评估了不同剂量的姜酮对 PCa 细胞系细胞凋亡、Akt/mTOR 等上游信号分子以及迁移和转移的疗效。使用 MTT 进行细胞活力测定,以估计姜酮处理的 PC-3 细胞的存活率百分比。通过使用不同的荧光染色技术研究了姜酮处理的 PC-3 细胞中线粒体膜电位、细胞内活性氧和细胞凋亡诱导。通过 Western blot 分析测定研究了 PI3K、AKT、p-AKT、mTOR 和 p-mTOR 的表达模式。姜酮诱导细胞凋亡并改变 Akt/mTOR 分子;它还抑制 PCa 细胞的粘附和迁移。从本研究中可以得出结论,姜酮有效地诱导细胞凋亡并抑制癌症信号,从而成为治疗 PCa 的有效药物。

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