PDF(Pubmed)
Abstract：
Few efficacious treatment options are available for patients with small cell lung carcinoma (SCLC), indicating the need to develop novel therapeutic approaches. In this study, we explored kinesin family member 11 (KIF11), a potential therapeutic target in SCLC. An analysis of publicly available data suggested that KIF11 mRNA expression levels are significantly higher in SCLC tissues than in normal lung tissues. When KIF11 was targeted by RNA interference or a small-molecule inhibitor (SB743921) in two SCLC cell lines, Lu-135 and NCI-H69, cell cycle progression was arrested at the G2/M phase with complete growth suppression. Further work suggested that the two cell lines were more significantly affected when both KIF11 and BCL2L1, an anti-apoptotic BCL2 family member, were inhibited. This dual inhibition resulted in markedly decreased cell viability. These findings collectively indicate that SCLC cells are critically dependent on KIF11 activity for survival and/or proliferation, as well as that KIF11 inhibition could be a new strategy for SCLC treatment.
摘要：
小细胞肺癌（SCLC）患者很少有有效的治疗选择。这表明需要开发新的治疗方法。在这项研究中,我们探索了驱动蛋白家族成员11(KIF11)，SCLC的潜在治疗靶点。对公开数据的分析表明，SCLC组织中的KIF11mRNA表达水平明显高于正常肺组织。当KIF11在两个SCLC细胞系中被RNA干扰或小分子抑制剂（SB743921）靶向时，Lu-135和NCI-H69，细胞周期进程在G2/M期停止，完全抑制生长。进一步的工作表明，当KIF11和BCL2L1，一个抗凋亡的BCL2家族成员，被抑制。这种双重抑制导致细胞活力显著降低。这些发现共同表明，SCLC细胞在存活和/或增殖方面严重依赖于KIF11活性。以及KIF11抑制可能是SCLC治疗的新策略。
