Department of Molecular Medicine, Research Institute for Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
Department of Medical Genome Sciences, Cancer Research Institute, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
Int J Mol Sci. 2024 Jun 30;25(13):7230. doi: 10.3390/ijms25137230.
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 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.
针对小细胞肺癌（SCLC）患者，目前有效的治疗选择有限，这表明需要开发新的治疗方法。在这项研究中，我们研究了驱动蛋白家族成员 11（KIF11），它是 SCLC 的一个潜在治疗靶点。对公开可用数据的分析表明，在 SCLC 组织中的 mRNA 表达水平明显高于正常肺组织。当用 RNA 干扰或小分子抑制剂（SB743921）靶向两种 SCLC 细胞系 Lu-135 和 NCI-H69 中的 KIF11 时，细胞周期停滞在 G2/M 期，完全抑制了细胞生长。进一步的研究表明，当同时抑制 KIF11 和抗凋亡 BCL2 家族成员 BCL2L1 时，这两种细胞系受到的影响更为显著。这种双重抑制导致细胞活力明显下降。这些发现共同表明，SCLC 细胞的存活和/或增殖严重依赖于 KIF11 的活性，并且抑制 KIF11 可能是治疗 SCLC 的一种新策略。
