组织蛋白酶B成熟通过激活NLRP3炎性小体在瘦素诱导的肝癌细胞生长中起关键作用

IF 6.9 3区 医学 Q1 CHEMISTRY, MEDICINAL
ThiKem Nguyen, Raut Pawan Kumar, Pil-Hoon Park
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引用次数: 1

摘要

瘦素是一种脂肪组织来源的激素,通过多种机制显示出强大的促肿瘤作用。组织蛋白酶B是溶酶体半胱氨酸蛋白酶的一员,已被证明可以调节癌细胞的生长。在这项研究中,我们研究了组织蛋白酶B信号在瘦素诱导的肝癌生长中的作用。瘦素治疗通过内质网应激轴和自噬诱导引起活性组织蛋白酶B水平的显著增加,而对组织蛋白酶B的前和前形态没有显著影响。有趣的是,通过基因沉默或选择性药理抑制剂(CA-074)治疗来抑制组织蛋白酶B信号传导,阻止了瘦素增强的肝癌细胞活力和抑制细胞周期的进展。表明组织蛋白酶B在瘦素诱导的肝癌生长中起关键作用。我们进一步观察到组织蛋白酶B的成熟是NLRP3炎性小体激活所必需的,这与肝癌细胞的生长有关。在体内HepG2肿瘤异种移植模型中证实了组织蛋白酶B成熟在瘦素诱导的肝癌生长和NLRP3炎性体激活中的关键作用。综上所述,这些结果表明,组织蛋白酶B信号通过激活NLRP3炎症小体在瘦素诱导的肝癌细胞生长中起关键作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Cathepsin B maturation plays a critical role in leptin-induced hepatic cancer cell growth through activation of NLRP3 inflammasomes

Cathepsin B maturation plays a critical role in leptin-induced hepatic cancer cell growth through activation of NLRP3 inflammasomes

Leptin, an adipose tissue-derived hormone, exhibits potent tumor promoting effects through various mechanisms. Cathepsin B, a member of the lysosomal cysteine proteases, has been shown to modulate the growth of cancer cells. In this study, we have investigated the role of cathepsin B signaling in leptin-induced hepatic cancer growth. Leptin treatment caused significant increase in the levels of active cathepsin B through the axis of endoplasmic reticulum stress and autophagy induction without significant effects on pre- and pro-forms of cathepsin B. Interestingly, inhibition of cathepsin B signaling by gene silencing or treatment with a selective pharmacological inhibitor (CA-074) prevented leptin-enhanced viability of hepatic cancer cell and suppressed progression of cell cycle, indicating the critical role of cathepsin B in leptin-induced hepatic cancer growth. We have further observed that maturation of cathepsin B is required for NLRP3 inflammasomes activation, which is implicated in the growth of hepatic cancer cell. The crucial roles of cathepsin B maturation in leptin-induced hepatic cancer growth and NLRP3 inflammasomes activation were confirmed in an in vivo HepG2 tumor xenograft model. Taken together, these results demonstrate that cathepsin B signaling plays a pivotal role in leptin-induced hepatic cancer cell growth by activating NLRP3 inflammasomes.

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来源期刊
CiteScore
13.40
自引率
9.00%
发文量
48
审稿时长
3.3 months
期刊介绍: Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.
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