Effects and Mechanisms of Saikosaponin D Improving the Sensitivity of Human Gastric Cancer Cells to Cisplatin.
Effects and Mechanisms of Saikosaponin D Improving the Sensitivity of Human Gastric Cancer Cells to Cisplatin.
复制标题
柴胡皂苷D提高人胃癌细胞对顺铂敏感性的作用及机制
DOI：
10.1021/acsomega.1c01795
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发表时间：
2021-07-27
期刊：
影响因子：
4.1
通讯作者：
Tie J
中科院分区：
文献类型：
--
作者：
Hu J;Li P;Shi B;Tie J
胃癌(GC)是全球第二大癌症死亡原因。化疗耐药是胃癌预后不良的重要原因。柴胡皂苷D(SSD)是柴胡的天然成分之一，具有抗肿瘤等多种活性。本研究探讨SSD对胃癌细胞顺铂(顺铂，DDP)敏感性的影响及其机制。结果提示，SSD可增强DDP对SGC-7901和DDP耐药细胞株SGC-7901/DDP增殖和侵袭的抑制作用，并增加DDP诱导的细胞凋亡。我们进一步证实，丹参汤能增加Lc3B和裂解caspase3的水平，降低p62、IKKβ、p-IκBα和NF-κB p65的水平，提示丹参可能抑制IKKβ/NF-κB通路，诱导SGC7901和SGC7901/DDP细胞的自噬和凋亡。进一步研究表明，丹参能增强顺铂诱导的caspase3裂解水平的升高和对NF-κB通路的抑制，尤其是对SGC7901/DDP细胞。结论：丹参提高了GC细胞对顺铂的敏感性，其可能的分子机制是通过诱导胃癌细胞的凋亡和自噬，抑制IKKβ/NF-κB通路。这些结果提示，SSD可能有助于克服GC治疗中的DDP耐药。
Gastric cancer (GC) is the second leading cause of cancer deaths around the world. Chemoresistance is an important reason for poor prognosis of GC. Saikosaponin D (SSD) is a natural constituent from Radix Bupleuri and exhibits various activities including antitumors. This study investigated the effects and the mechanisms of SSD on cisplatin (cis-diamminedichloroplatinum, DDP) sensitivity of GC cells. Findings suggested that SSD could promote the inhibitory effect of DDP on proliferation and invasion and increase DDP-induced apoptosis in SGC-7901 and DDP-resistant cell line SGC-7901/DDP. We further identified that SSD increased levels of LC3 B and cleaved caspase 3 and decreased levels of p62, IKK β, p-IκB α, and NF-κB p65, suggesting that SSD might inhibit the IKK β/NF-κB pathway and induce both cell autophagy and apoptosis in SGC-7901 and SGC-7901/DDP. A further study indicated that SSD enhanced the effect of DDP-induced cleaved caspase 3 level rise and NF-κB pathway suppression, especially in SGC-7901/DDP cells. Conclusively, SSD enhanced DDP sensitivity of GC cells; the potential molecular mechanisms were that SSD-induced apoptosis and autophagy and inhibited the IKK β/NF-κB pathway in GC cells. These findings suggested that SSD might contribute to overcoming DDP resistance in GC treatment.
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DOI：
10.2147/dddt.s90081
发表时间：
2016
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Jin R;Xia Y;Chen Q;Li W;Chen D;Ye H;Zhao C;Du X;Shi D;Wu J;Liang G
通讯作者：
Liang G
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
5.1
作者：
Cui, Li-Hua;Li, Cai-Xia;Zhang, Shu-Kun
通讯作者：
Zhang, Shu-Kun
影响因子：
4
作者：
Liu, Yinghui;Lei, Hongbo;Dong, Weiguo
通讯作者：
Dong, Weiguo
影响因子：
4.7
作者：
Manu, Kanjoormana A.;Shanmugam, Muthu K.;Sethi, Gautam
通讯作者：
Sethi, Gautam