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Archive > Volume 33 Issue 5 > 2026,33(5):500-509. DOI:10.3872/j.issn.1007-385X.2026.05.004 Prev Next
Basic Research
Small-molecule compound WAY-312 inhibits proliferation and self-renewal of glioblastoma stem cells through cell cycle arrest and apoptosis induction
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Abstract:
[Abstract] Objective：This study investigated the inhibitory activity and potential mechanism of WAY-312, a small-molecule compound derived through screening of a small-molecule compound library, against the growth and self-renewal capacity of glioblastoma stem cells (GSCs). Methods: Systematic compound screening was conducted on the small molecule compound library through tumor sphere formation assays and cell viability assays; the small molecule inhibitor WAY-302386 (named WAY-312 according to its compound number) obtained through screening was used as the research object. CCK-8 method, Western blot, flow cytometry, and Caspase-Glo 3/7 activity detection method were used to detect the effects of WAY-312 on the proliferation ability, stemness marker expression, cell cycle distribution, and apoptosis level of glioblastoma stem cells at different concentrations. The regulatory effect of WAY-312 on GSC stemness maintenance and self-renewal ability was clarified, and the mechanism of WAY-312 on GSC cell cycle progression and apoptosis was further elucidated. Results: WAY-312 can effectively inhibit the survival of GSCs (P < 0.05); WAY-312 significantly inhibits the number and size of tumor spheroids formed in GSCs (P < 0.05), and treatment with WAY-312 reduces the expression levels of stemness marker proteins SOX2, OLIG2, and BMI1; WAY-312 can effectively inhibit the self-renewal ability of GSCs (P < 0.05); WAY-312 induces GSC cell cycle arrest at the G2/M phase by regulating the expression of cell cycle-related proteins Cyclin B1, CDK4, and CDK6 (P < 0.05); WAY-312 induces apoptosis in GSCs, increases the expression of apoptosis-related proteins cleaved-PARP and BAX, reduces the expression of BCL2, and enhances Caspase-3/7 activity in GSCs after treatment with WAY-312. Conclusion: WAY-312 can inhibit GSC proliferation, stemness maintenance, and self-renewal ability, induce GSC cell cycle arrest at · · 500 车虹宇, 等. 小分子化合物WAY-312通过周期阻滞与凋亡诱导抑制胶质母细胞瘤干细胞增殖及自我更新 G2/M phase, and promote cell apoptosis in a concentration-dependent manner.
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