Nampt抑制剂对乳腺癌细胞化疗增敏作用的研究

Study of Nampt-inhibitor-based chemosensitization effects in 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,及Nampt抑制剂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Nampt mRNA表达水平,并用噻唑蓝(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 qRT-PCR结果表明,乳腺癌组织内Nampt mRNA表达高于癌旁正常组织中的表达3.5倍,差异有统计学意义(P<0.05)。经FK866干预24 h,细胞的生长没有明显的抑制;但在48 h、72 h后,FK866(3~30 nmol/L)干预MCF-7细胞出现生长的抑制。随FK866的浓度增加,细胞克隆球数逐渐减少,相邻干预浓度的两组间比较,差异有统计学意义(均P<0.01)。结论 Nampt抑制剂能影响乳腺癌细胞生长,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 investigate the effects of Nampt inhibitor on the growth and chemotherapy sensitivity of breast cancer cells. Methods Nampt mRNA expressions in breast cancer tissues and adjacent normal tissues were detected by qRT-PCR method ; the effect of Nampt inhibitor on the growth of breast cancer cells and chemosensi- tization was detected by methyl thiazolyl tetrazolium （MTT） and soft agar clonogenic assays. Results qRT- PCR showed that Nampt in breast cancer tissues was significantly higher than that in adjacent normal breast tis- sues （3 folds, P 〈 O. 05 ）. After 24 h of FK866 intervention, there was no significant inhibition of cell growth, however, after 48 h and 72 h, FK866 （ 3 - 30 nmol/L） inhibited the proliferation of MCF-7 cells. With the in- crease of FK866 concentration, the number of cell clones decreased gradually, and there was significant differ- ence between two adjacent intervention concentration groups （all P 〈 O. 01 ）. Conclusions Our findings indi- cate that Nampt may be a new therapeutic target for breast cancer, and combined therapy of Nampt and eytotoxic drugs has the effect of chemosensitization.