Synergistic effects of a novel lipid-soluble extract from Pinellia pedatisecta Schott and cisplatin on human cervical carcinoma cell lines through the regulation of DNA damage response signaling pathway.
Synergistic effects of a novel lipid-soluble extract from Pinellia pedatisecta Schott and cisplatin on human cervical carcinoma cell lines through the regulation of DNA damage response signaling pathway.
复制标题
新型半夏脂溶性提取物和顺铂通过调节DNA损伤反应信号通路对人宫颈癌细胞系的协同作用
DOI：
10.3892/ol.2017.5738
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发表时间：
2017-04
期刊：
影响因子：
2.9
通讯作者：
Xu C
中科院分区：
文献类型：
--
作者：
Zhang M;Zhang H;Yu Y;Huang H;Li G;Xu C
草药已被认为是一种有吸引力的癌症治疗方法，副作用最小。研究掌叶半夏脂溶性提取物（PE）与顺铂（CDDP）在体外对人宫颈癌SiHa和CaSki细胞系的相互作用。使用细胞增殖、侵袭和凋亡测定，并通过分析细胞周期分布和蛋白质表达，重点是DNA损伤反应（DDR）激活，研究了这种组合的机制。通过等效线图分析确定PE和CDDP的等效组合，以评估潜在的协同作用。SiHa细胞的联合指数为0.43，CaSki细胞的联合指数为0.68，表明具有协同作用。PE和CDDP联合治疗对两种细胞侵袭的抑制作用均显著高于单独治疗（SiHa，P<0.01; CaSki，P<0.001）。SiHa和CaSki细胞分别阻滞于G 0/G1期和G2/M期，S期细胞明显减少（P<0.01）。联合PE和CDDP靶向协同增强细胞中DDR标志物（共济失调-毛细血管扩张症突变的磷酸化、检查点激酶（Chk）-1，Chk-2和γ-H2 A组蛋白家族成员X）的表达。这些结果表明，PE和顺铂在具有高DDR激活的宫颈癌细胞中具有协同作用。本研究为掌叶半夏的药理作用机制及宫颈癌的治疗提供了新的思路。
Herbal medicines have been recognized as an attractive approach for cancer therapy with minimal side effects. The present study investigated the type of interaction between a novel lipid-soluble extract from Pinellia pedatisecta Schott (PE) and cisplatin (CDDP) on human cervical cancer SiHa and CaSki cell lines in vitro. The mechanism of this combination was studied using cell proliferation, invasion and apoptosis assays, and by analyzing cell cycle distribution and protein expression, with a focus on DNA damage response (DDR) activation. Equipotent combinations of PE and CDDP were determined by isobologram analysis, in order to evaluate potential synergy. The combination index for SiHa cells was 0.43, and the index for CaSki cells was 0.68, indicating synergy. Treatment with PE and CDDP combined resulted in a significantly greater inhibition of invasion in the two cells, compared with either drug alone (SiHa, P<0.01; CaSki, P<0.001). This co-treatment induced significantly more apoptosis in the two cell lines, and arrested cells at the G0/G1 phase and G2/M phase in SiHa and CaSki, respectively, with a significant decrease (P<0.01) in S phase cells in the two cell lines. Combined PE and CDDP targeting synergistically enhanced the expression of markers of DDR (phosphorylation of ataxia-telangiectasia mutated, checkpoint kinase (Chk)-1, Chk-2, and γ-H2A histone family member X) in cells. These results suggest that PE and cisplatin act synergistically in cervical cancer cells with high DDR activation. The approach presented in the present study may have important implications for the pharmacological mechanism of Pinellia pedatisecta Schott and cervical cancer therapeutic strategies.