| 郭崇勇1 柯卫锋1 宋科瑛1 王建丰1 周凌2 李克1.PI3K/AKT 通路参与调控乳腺癌多药耐药和侵袭转移的研究[J].现代生物医学进展英文版,2012,12(25):4809-4812. |
| PI3K/AKT 通路参与调控乳腺癌多药耐药和侵袭转移的研究 |
| PI3K/AKT Signalling Pathway Involves in the Modulation of MultidrugResistance and Metastasis in Breast Cancer |
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| DOI： |
| 中文关键词: 乳腺肿瘤 耐药性 转移 PI3K/AKT |
| 英文关键词: Breast neoplasms Resistance Metastasis PI3K/ AKT |
| 基金项目: |
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| 中文摘要: |
| 目的：探讨磷脂酰肌醇-3- 激酶/ 丝苏氨酸蛋白激酶（phosphatidylinositol 3 kinase/serine-threonine kinase,PI3K/AKT）信号通
路与乳腺癌多药耐药和侵袭转移的相关性。方法：以乳腺癌细胞系MCF-7 为母本，持续低浓度加药诱导建立阿霉素（Adriamycin,
ADR）耐药系MCF-7/ADR'。细胞免疫荧光检测两细胞系中磷酸化AKT(phosphorylated AKT, P-AKT)、P- 糖蛋白（P-Glycoprotein,
P-gp）、基质金属蛋白酶2（matrix metalloproteinase-2，MMP-2）的表达。PI3K 抑制剂LY294002 作用两系前后，Western Blot 检测
P-AKT、MMP-2、P- gp 的表达改变及qRT-PCR 检测MMP-2、MDR1 的表达改变。结果：P-AKT、P-gp(MDR1)、MMP-2 在MCF-7 中
为低表达或不表达，MCF-7/ADR' 中为高表达。LY294002 作用两系后，P-AKT、P- gp(MDR1)、MMP-2 在MCF-7/ADR' 中的表达明
显减低（P<0.05），MCF-7 无明显改变。结论：抑制PI3K/AKT 信号通路可有效降低MCF-7/ADR' 耐药和侵袭转移能力，PI3K/AKT
通路是调控乳腺癌多药耐药和侵袭转移的重要信号通路之一。 |
| 英文摘要: |
| Objective: To study the relationship between phosphatidylinositol 3 kinase/serine-threonine kinase (PI3K/AKT）
signalling pathway and the resistance or invasive ability of breast cancer. Methods: MCF-7/ADR' were established by culturing parental
MCF-7 cells with increasing concentration of adriamycin. The expression of phosphorylated AKT (P-AKT), P-Glycoprotein (P-gp) and
matrix metalloproteinase-2(MMP-2) was investigated by Immunofluorescence assay. The expression of P-AKT, P-gp and MMP-2 with or
without treatment of the PI3K inhibitor LY294002 was investigated by Western blot assay. Real-time quantitative PCR assay was used to
investigate the expression of MDR1 and MMP-2. Results: In MCF-7 cells, P-AKT, P-gp (MDR1) and MMP-2 were neither detected nor
only weakly expressed. In MCF-7/ADR' cells, the expression of P-AKT, P-gp (MDR1) and MMP-2 was increased. Treatment of
MCF-7/ADR' cells with LY294002 can seriously reduced the expression of P-AKT, P-gp (MDR1) and MMP-2. Significant differences
were not observed in MCF-7 cells. Conclusion: The resistance and metastasis can be reduced significantly through suppression of the
PI3K/AKT signalling pathway. PI3K/AKT kinase pathway may be important in the modulation of resistance and metastasis in breast
cancer. |
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