Department of Hepatobiliary and Pancreas Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Department of Biochemistry, Basic College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
Int J Oncol. 2017 Nov;51(5):1383-1394. doi: 10.3892/ijo.2017.4134. Epub 2017 Sep 22.
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.
胃癌被报道为导致全球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，而且耐药性的出现使得开发新的有效抗癌药物和联合化疗方案成为必要。甘草素（LIQ）是甘草根的主要成分之一，具有多种药理活性，包括抗癌作用。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。研究结果表明，LIQ 在单一治疗中可适度抑制 DDP 耐药胃癌细胞 SGC7901/DDP 的增殖和迁移。DDP 和 LIQ 联合应用诱导 G0/G1 细胞周期停滞，抑制胃癌细胞增殖，这与细胞周期蛋白 D1、细胞周期蛋白 A 和细胞周期蛋白依赖性激酶 4（CDK4）的减少以及 p53 和 p21 的增加有关。此外，LIQ 联合 DDP 通过增强半胱天冬酶-8/-9/-3 和多聚（ADP-核糖）聚合酶（PARP）的裂解，以及 LC3B 和 Beclin 1 的表达，在体外和体内显著诱导凋亡和自噬。重要的是，这两种药物联合应用可预防裸鼠体内胃癌细胞异种移植物的生长。总之，研究结果表明，DDP 和 LIQ 的联合应用具有针对 DDP 耐药人胃癌生长的潜在价值。
