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目的明确脂肪酸合成酶(FAS)在人多发性骨髓瘤(MM)细胞中的高表达;探讨 FAS 抑制剂抑制 MM 细胞增殖及诱导其凋亡的机制。方法通过 RT-PCR 方法检测 FAS 在 MM 细胞系U266、RPMI8226细胞中的表达;以 MM 细胞系 U266细胞为模型,MTT 法观察 FAS 抑制剂浅蓝菌素(cerulenin)对 U266细胞增殖抑制率;以流式细胞术检测经 cerulenin 处理后 U266细胞 Annexin V 的表达及细胞周期变化。结果 MM 细胞系 U266、RPMI8226细胞均有 FAS mRNA 的高表达,而健康献血员外周血单个核细胞(PBMNC)中不表达 FAS mRNA;cerulenin 对 U266细胞增殖有显著的抑制作用,并呈剂量-效应相关;20μg/ml 的 cerulenin 作用于 U266细胞12h,细胞早期凋亡率为56.9%,24h 细胞早期凋亡率为69.3%,而对照组分别为4.3%和1.8%(P<0.01);细胞周期 DNA 分析发现,20μg/mlcerulenin 作用于 U266细胞12h,S 期细胞从对照组的9.7%上升至20.3%,作用24h,S 期细胞上升为29.8%。结论 FAS 在 MM 细胞中高表达;FAS 抑制剂可抑制 U266细胞的增殖;DNA 合成阻止在 S期,其抑制增殖的作用可能是通过促进 U266细胞早期凋亡;FAS 可能是一个潜在的抗 MM 的靶位。
Objective To determine the high expression of fatty acid synthase (FAS) in human multiple myeloma (MM) cells and to explore the mechanism of FAS inhibitors inhibiting the proliferation and inducing apoptosis of MM cells. Methods The expression of FAS in MM cell line U266 and RPMI8226 cells was detected by RT-PCR. The inhibition rate of FAS inhibitor Cerulenin on the proliferation of U266 cells was observed by MTT assay in MM cell line U266 cells. Flow cytometry was used to detect the expression of Annexin V and the cell cycle in U266 cells treated with cerulenin. Results FAS mRNA was highly expressed in both U266 and RPMI8226 cells, while FAS mRNA was not expressed in peripheral blood mononuclear cells (PBMNC) from healthy blood donors. Cerulenin significantly inhibited the proliferation of U266 cells in a dose-response manner The early apoptosis rate of U266 cells was 56.9% at 20μg / ml for 12 hours, and the early apoptosis rate was 69.3% in U266 cells compared with 4.3% and 1.8% in control group (P <0.01) DNA analysis showed that 20μg / mlcerulenin increased the percentage of S phase cells to 12.3% in U266 cells from 9.7% in control cells at 12h, and increased to 29.8% in S phase at 24h. Conclusion FAS is overexpressed in MM cells. FAS inhibitor can inhibit the proliferation of U266 cells. DNA synthesis inhibits the inhibition of proliferation in S phase by promoting the early apoptosis of U266 cells. FAS may be a potential anti-MM target Bit.