Liquiritin induces apoptosis and autophagy in cisplatin (DDP)-resistant gastric cancer cells in vitro and xenograft nude mice in vivo.

Liquiritin induces apoptosis and autophagy in cisplatin (DDP)-resistant gastric cancer cells in vitro and xenograft nude mice in vivo.
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DOI:
10.3892/ijo.2017.4134
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发表时间:
2017-11
影响因子:
5.2
通讯作者:
Gao SH
Gao SH
中科院分区:
医学2区
文献类型:
--
作者:
Wei F;Jiang X;Gao HY;Gao SH

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据报道,胃癌是世界范围内导致肿瘤相关死亡的主要因素之一。然而,抑制胃癌的治疗方法仍然有限,耐药的出现使得开发新的有效的抗癌药物和联合化疗方案成为必要。甘草素(Liquiritin,LIQ)是甘草的主要成分之一,具有包括抗癌在内的多种药理活性。在这项研究中,我们研究了LIQ在顺铂(DDP)耐药的人胃癌细胞中的作用。提示LIQ单药治疗可适度抑制耐DDP的胃癌细胞SGC7901/DDP的增殖和迁移。DDP和LIQ联合应用可诱导G0/G1期细胞周期停滞,从而抑制胃癌细胞的增殖,其机制与细胞周期蛋白D1、细胞周期蛋白A和细胞周期蛋白依赖性激酶4(CDK4)的表达减少、p53和p21的表达增加有关。此外,LIQ联合DDP在体内外均可通过促进caspase-8/-9/-3和PARP的裂解以及LC3B和Beclin 1的表达而显著诱导细胞凋亡和自噬。值得注意的是,当两种药物联合使用时,可以在体内阻止胃癌细胞在裸鼠体内的移植。以上结果表明,DDP和LIQ联合应用对顺铂耐药人胃癌的生长具有潜在的抑制作用。
Gastric cancer is reported as one of the leading factors resulting in tumor-related death worldwide. However, the therapies to suppress gastric cancer are still limited and the emergence of drug resistance makes it necessary to develop new and effective anticancer drugs and combinational chemotherapy schemes. Liquiritin (LIQ) is a major constituent of Glycyrrhiza Radix, exhibiting various pharmacological activities, including anticancer. In this study, we investigated the role of LIQ in human gastric cancer cells with cisplatin (DDP) resistance. The findings suggested that LIQ, when applied in single therapy, could moderately inhibit the proliferation and migration of DDP-resistant gastric cancer cells, SGC7901/DDP. DDP and LIQ in combination induced G0/G1 cell cycle arrest to suppress the proliferation of gastric cancer cells, which were associated with the decrease of cyclin D1, cyclin A and cyclin-dependent kinase 4 (CDK4) and increase of p53 and p21. In addition, LIQ combined with DDP significantly induce apoptosis and autophagy both in vitro and in vivo through enhancing cleavage of caspase-8/-9/-3 and PARP, as well as LC3B and Beclin 1 expression. Significantly, the two drugs, when used in combination, prevented gastric cancer cell xenografts in nude mice in vivo. Together, the results revealed that application of DDP and LIQ in combination possessed a potential value against the growth of human gastric cancer with DDP resistance.
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