磷酯酰肌醇3激酶抑制剂对三阴性乳腺癌细胞增殖及迁移的影响

Effects of phosphoinositide 3-kinase inhibitor on the proliferation and migration of triple-negative breast cancer cell lines

摘要:

目的：为了研究磷脂酰肌醇3激酶（phosphoinositide 3 kinase，PI3K）抑制剂单用及其联合表皮生长因子受体（epidermal growth factor receptor，EGFR）抑制剂对三阴性乳腺癌（triple-negative breast cancer，TNBC）细胞增殖、迁移的影响。方法：通过细胞增殖实验、克隆形成实验、细胞划痕愈合实验、流式细胞仪以及ELISA实验来分析PI3K抑制剂PF-04691502（以下简写为PF）单用或与EGFR抑制剂吉非替尼联合抗TNBC细胞（HCC1937和MDA-MB 231）增殖、迁移的的影响。结果：PF可显著抑制TNBC细胞的增殖，对TNBC细胞克隆的形成、迁移和蛋白激酶Ｂ[（protein kinase B，PKB），又名Akt]的磷酸化均有显著抑制作用（P<0.0５），并可将TNBC细胞阻滞于G1期（P<0.0５）。小剂量PF联合EGFR抑制剂吉非替尼可协同抑制TNBC细胞的增殖、克隆形成、迁移及Akt的磷酸化。结论：PI3K抑制剂单用可显著抑制TNBC细胞的增殖、克隆形成和迁移，与EGFR抑制剂合用可形成明显的协同效应。其作用机制可能与其降低Akt磷酸化水平及G1期细胞周期阻滞作用有关。

Abstract:

Objective：To study the effects of phosphoinositide 3kinase（PI3K） inhibitor alone and in combination with epidermal growth factor receptor（EGFR） inhibitor on the proliferation and migration of triple-negative breast cancer（TNBC） cell lines. Meth－ods：Effects of PF-04691502（PF），a PI3K inhibitor，alone or in combination with gefitinib，a EGFR inhibitor，on the proliferation and migration of TNBC cell lines（HCC1937 and MDA-MB 231） were measured by the proliferation，colony formation，wound-healing，flow cytometry and ELISA. Results：PF prevented the proliferation，colony formation and migration of TNBC cell lines，inhibited the protein kinase B（ＰＫＢ or Akt） phosphorylation of these cell lines and retarded the cells in G1 phase（P<0.0５）. Significant synergistic effects were observed when in combination with gefitinib，a EGFR inhibitor. Conclusions：PI3K inhibitor when used alone could pre－vent the proliferation，colony formation and migration of TNBC cell lines and when used in combination with EGFR inhibitors could form significant synergistic effects，mechanisms of which may relate with it’s inhibition of Akt phosphorylation and G1 phase arrest.