JD enhances the anti-tumour effects of low-dose paclitaxel on gastric cancer MKN45 cells both in vitro and in vivo
JD enhances the anti-tumour effects of low-dose paclitaxel on gastric cancer MKN45 cells both in vitro and in vivo
复制标题
JD增强小剂量紫杉醇对胃癌MKN45细胞体内外的抗肿瘤作用
DOI：
10.1007/s00280-016-3149-9
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发表时间：
2016-11-01
影响因子：
3
通讯作者：
Liu, Hongmin
中科院分区：
文献类型：
--
作者：
Wang, Cong;Wang, Ran;Liu, Hongmin
背景胃癌是世界范围内第三大恶性肿瘤死亡原因，紫杉醇（paclitaxel，PTX）是治疗胃癌最常用的传统药物之一。然而，对传统疗法的反应受到获得性化疗耐药性和副作用的限制。在这里，我们建立了一个新设计的组合疗法组成的化合物，是一个结构变异的冬凌草甲素，即Jesridonin（JD），和低剂量的PTX胃癌细胞（MKN 45），以调查是否低剂量的PTX的抗肿瘤活性可以增强时，结合JD.MethodsThe JD和低剂量的PTX的相互作用，检测在MKN 45细胞中使用的中效分析方法。通过MTT法、克隆形成实验、瞬时转染、流式细胞术和Western blotting检测对细胞活力和凋亡的协同作用。采用H&E法、TUNEL染色法和Western blotting法观察JD与小剂量PTX联合应用对裸鼠移植瘤的体内协同作用。此外，JD和低剂量PTX的组合检测到协同抗增殖和促凋亡作用。JD加PTX诱导的细胞凋亡机制表明，联合治疗协同激活线粒体pathway.ConclusionOur研究结果表明，JD增强了低剂量PTX对胃癌细胞的抗肿瘤作用在体外和体内，伴随着线粒体通路的激活，这可能是一个更有效的治疗策略，在胃癌治疗。
BackgroundGastric cancer is the third most common cause of cancer mortality worldwide, and paclitaxel (PTX) is one of the most widely used traditional drugs in gastric cancer therapy. However, the response to traditional therapy is limited by acquired chemo-resistance and side effects. Here, we establish a newly designed combination therapy consisting of a compound that is a structural variant of oridonin, i.e. Jesridonin (JD), and low-dose PTX for gastric cancer cells (MKN45) to investigate whether the anti-tumour activity of low-dose PTX could be enhanced when combined with JD.MethodsThe interaction of JD and low-dose PTX was detected in MKN45 cells using the median-effect analysis method. The synergistic effect on cell viability and apoptosis was measured by MTT assay, colony formation assay, transient transfection, flow cytometry and Western blotting. The synergistic in vivo effect of JD plus low-dose PTX was evaluated in nude mouse xenograft models using H&E and TUNEL staining and Western blotting.ResultsJD plus low-dose PTX showed a synergistic effect, as the combination indexes were less than 1. Additionally, a synergistic anti-proliferative and pro-apoptotic effect was detected for the combination of JD and low-dose PTX. The apoptotic mechanism induced by JD plus PTX revealed that the combination therapy synergistically activated the mitochondrial pathway.ConclusionOur findings suggest that JD enhances the anti-tumour effect of low-dose PTX on gastric carcinoma cancer cells in both vitro and in vivo, accompanied by activation of the mitochondrial pathway, which may present a more effective therapeutic strategy in gastric cancer treatment.