雷公藤内酯醇阳离子聚合物肝细胞毒性及其对乳腺癌干细胞影响的研究

Exploration for the Toxicity of TPL-PEI-CyD to Hepatocytes and Effects on Breast Cancer Stem Cells

该文观察了雷公藤内酯醇阳离子聚合物(TPL-PEI-Cy D)对乳腺癌干细胞的影响。采用CCK-8测定TPL-PEI-Cy D、雷公藤内酯醇(TPL)对HL-7702细胞的毒性,用TGF-β1孵育培养MCF-7细胞,流式细胞仪检测其中CD_(44)^+CD_(24)~–标志的细胞比例;免疫磁珠法分选其中CD_(44)^+CD_(24)~–细胞群;TPL-PEI-Cy D作用于MCF-7干细胞后,流式细胞术检测其中CD_(44)^+CD_(24)~–细胞比例的变化。雷公藤内酯醇在接入聚乙烯亚胺–环糊精后,对肝细胞的毒性较雷公藤内酯醇单体显著降低(P<0.05),用TGF-β1培养能富集高比例的乳腺癌干细胞;免疫磁珠分选法从中分离出肿瘤干细胞;TPL-PEI-Cy D较TPL更高效地抑制MCF-7干细胞后中CD_(44)^+CD_(24)~–细胞的比例(P<0.05)。结果说明,TPL-PEI-Cy D的肝细胞毒性降低且能高效地抑制乳腺癌干细胞的性能,有望开发成为治疗乳腺癌的中药新制剂。

The purpose of this study was to survey the effects of TPL-PEI-Cy D on breast carcinoma stem cells. The cytotoxicity of TPL-PEI-Cy D and TPL on HL-7702 was compared by CCK-8. After incubation and culturing by TGF-β1, the MCF-7 cells were assessed by flow cytometry for the proportion of CD（44）＋CD（24）– cells; Then, sorted the CD（44）＋CD（24）– cells by magnetic-activated cell sorting as MCF-7 stem cells. MCF-7 stem cells were dosed by TPL-PEICy D and then assessed by double staining flow cytometry for the variation of CD（44）＋CD（24）– proportion. Compared with TPL, the toxicity of TPL-PEI-Cy D on liver cells was significantly declined（P〈0.05）. Breast carcinoma stem cells could be enriched by TGF-β1 and isolated from MCF-7 cells with immunomagnetic sorting. After dosed with TPL-PEI-Cy D, the proportion of CD（44）＋CD（24）– in MCF-7 stem cells was significantly lower than dosed with TPL（P〈0.05）. TPL-PEICy D could effectively suppress the property of breast carcinoma stem cell. It showed the unique effect of traditional Chinese medicine as a efficient and low toxic drug carrier complex for breast carcinoma treatment.