烟酰胺磷酸核糖基转移酶抑制剂对乳腺癌细胞化疗增敏的影响

Nampt-inhibitor-based chemopotentiating effects on breast cancer cells

目的探讨乳腺癌组织及癌旁正常乳腺组织中烟酰胺磷酸核糖基转移酶（Nampt）的表达并确定Nampt抑制剂FK866对乳腺癌细胞生长和化疗增敏的影响。方法采用qRT-PCR法检测乳腺癌组织和癌旁正常组织中NamptmRNA表达水平，并用MTT实验和软琼脂克隆形成实验检测Nampt抑制剂对乳腺癌细胞生长的影响和对其化疗增敏的作用。结果乳腺癌组织内NamptmRNA表达水平显著高于癌旁正常组织中的表达（P=0．000）；FK866干预细胞48h和72h后，FK866即对MCF-7细胞生长产生明显的抑制作用（P=003；P=0．001）；FK866能抑制乳腺癌细胞克隆集落形成，相邻干预浓度的2组间（0．3nMvs 0nM；3nMvs0．3nM；30nMvs3nM）差异均有统计学意义（P值分别=0．02、0．014、0．02）。且FK866能增加5-FU对乳腺癌细胞的化疗敏感性。结论Nampt抑制剂能影响乳腺癌细胞生长，其与细胞毒药物联合应用具有化疗增敏作用。

Objective To study the expression of nicotinamide phosphoribosyl transferase （Nampt） in breast cancer and to investigate the effects of Nampt inhibitor on the growth and chemotherapy sensitivity of breast cancer cells. Methods Nampt mRNA expression in breast cancer tissues and adjacent normal tissues was detected by qRT-PCR method. The effect of Nampt inhibitor on the growth of breast cancer cells and chemothera- py sensitization was detected by M3T and soft agar clonogenic assays. Results Nampt in breast cancer was sig- nificantly higher than that in normal breast tissue （P=0.000）. Nampt inhibitor FK866 repressed breast cancer cell proliferation （24 h, P=0.003; 48 h, P=-0.001 ） and suppressed cell anchorage-independent growth （0.3 nM vs 0 nM, P=0.02; 3 nM vs 0.3 nM, P=0.0143; 0 nM vs 3 nM, P=0.02）. FK866 also increased the chemo-sensitivity of breast cancer cells to fluorouracil by greater inhibition of cell proliferation. Conclusion Our findings indicate that Nampt may be a new therapeutic target for breast cancer.