芪薏术蝎方不同提取物对三氯卡班引起乳腺上皮细胞癌变的修复作用

[目的]本文旨在研究芪薏术蝎方不同提取物对癌变细胞的修复作用。[方法]以芪薏术蝎方水提物、多糖提取物和醇提物3种药物为试验药物，以紫杉醇为阳性对照药物，以三氯卡班（triclocarban，TCC）单独长期处理细胞为阳性对照，以正常乳腺上皮细胞（EpH4-Ev）为阴性对照，以各药物的最大安全浓度为有效工作浓度，将药物和TCC同时加入到EpH4-Ev单层细胞中，以暴露48 h为1个循环周期，连续重复6个周期（T-6）后测定细胞增殖率、细胞内ROS水平、细胞内ERK通路的活化程度、DNA双链断裂程度、细胞的总凋亡率以及非停泊性生长和细胞迁移率等癌症相关的指标，评估药物对TCC长期暴露处理所致细胞癌变的影响。[结果]与阳性对照细胞相比，4种药物均能够显著抑制长期暴露于TCC的细胞发生非停泊性生长和细胞迁移；细胞内ROS水平显著升高，DNA双链断裂程度以及细胞的总凋亡率均显著升高；各药物组细胞增殖率显著下降，细胞内ERK通路的活化程度受到显著抑制。各提取物多数指标优于紫杉醇。[结论]芪薏术蝎方提取物与紫杉醇均能通过促进癌变细胞产生大量的ROS，从而引起细胞增殖抑制，ERK通路抑制，促进癌变细胞DNA损伤和细胞凋亡，最终修复由TCC诱导形成的癌变细胞。
[Objectives] The paper aimed to estimate the therapeutical effect of Qiyizhuxie formula’s extracts on cancerous cells. [Methods] We used three extracts of Qiyizhuxie formula as tested drugs, paclitaxel (PTX)as positive drug control, and the EpH4-Ev cell as negative control, the EpH4-Ev cell treated by triclocarban (TCC)in a long term as the positive cell control. In this experiment, the drugs at their maximal safe concentrations as effective concentrations and TCC were added simultaneously into EpH4-Ev monolayer. EpH4-Ev cultures were treated with TCC and these drugs simultaneously for 48 h as one cycle, and this treatment was repeated 6 cycles. Then the cell proliferation, ROS level, the activation of ERK pathway, DNA damage and cell apoptosis were detected, also the two cancer-associated properties including anchorage-independent growth (AIG)and cell mobility were measured. [Results] The results showed that compared to the positive cell control, these drugs were all effective on inhibiting the TCC-induced cellular acquisition of the scratch assay and AIG, also the ROS level, the extent of DNA double-stranded breaks and cell apoptosis were further intensified significantly. However, the cell proliferation and the degree of the p-ERK1/2 in drug groups were significantly reduced. Most of the above indexes in the extracts were better than those of the PTX. [Conclusions] These phenomena suggested that Qiyizhuxie formula and its extracts, and PTX induced cancerous cells to generate the ROS level excessively so that the cell proliferation and the activation of the ERK pathway were decreased, and the DNA damage and cell apoptosis were aggravated, thus to repair the cancerous cells induced by TCC in a long term