磷脂酶C-γ1对乳腺癌细胞增殖、粘附及迁移的作用

Effects of inhibiting phospholipase C-γ1 on proliferation and migration of breast cancer cells

目的探讨磷脂酶C-γ1(phospholipase C-γ1,PLC-γ1)对乳腺癌细胞生长、粘附和迁移等生物学行为的影响,揭示乳腺癌发生的分子机制。方法在乳腺癌细胞株MDA-MB-231中加入PLC-γ1抑制剂(U-73122),用MTT试验、划痕试验、细胞粘附及趋化运动试验检测细胞生物学行为的变化,western blot检测抑制PLC-γ1后的信号传导通路中整合素β1和PKCζ分子磷酸化激活的情况。结果 PLC-γ1被U-73122抑制后MDA-MB-231细胞的增殖、粘附和迁移运动能力下降,差异均有统计学意义(P<0.05)。western blot结果表明,细胞粘附相关整合素β1的磷酸化激活水平降低;趋化运动相关PKCζ磷酸化水平降低。结论 PLC-γ1参与调控乳腺癌细胞增殖、粘附和迁移运动,可能是乳腺癌分子诊断和靶向治疗的有效靶点。

Abstract： Objective To study the effects of phospholipase C-γl as a potential regulator on the biological behaviors of breast cancer ceils, e. g. , proliferation, adhesion, migration, etc. , and explore the molecular mechanisms of breast cancer development. Methods Variation of PLC-5,1 expression level of human breast cancer cell line MDA-MB-231 was observed by adding PLC-γ1 inhibitor U- 73122. The cellular biological behaviors were tested by M3T assay, scratch test, cellular chemotaxis and adhesion test. The level of phosphorylated integrin 131 and protein kinase C （PKC） in the intracellular signal transduction pathways were detected by western blot. Results The proliferation, migration and adhesion of MDA-MB-231 cells decreased following the inhibition of MDA-MB-231 cells by PLC-γ1 inhibitor U-73122 （P 〈 0.05）. The phosphorylation levels of integrin β1 and PKC[ reduced. Conclusion PLC-γ1 inhibition dampened proliferation, migration and adhesion of breast cancer cells, and might serve as an effective strategy for molecular diagnosis and targeted therapy of breast cancer.