p70S6K1在结直肠癌中的作用及潜在分子机制（英文）

Effects of p70S6K1 in Colorectal Cancer and Related Mechanism

目的探讨p70S6K1在结直肠癌(CRC)中的潜在分子机制及其与蟾蜍灵的相互作用。方法运用免疫组织化学染色方法验证p70S6K1在CRC组织中的表达量变化,并探讨其与CRC患者预后的关联性;利用p70S6K1的抑制剂PF-4708671分别通过MTT、β-半乳糖苷酶染色、细胞周期及划痕实验来检测PF-4708671对细胞生长、细胞衰老、细胞周期和细胞迁移的影响;在CRC细胞中使用蟾蜍灵,观察其对细胞生长及p70S6K1表达水平的影响。结果与正常对照相比,CRC组织中p70S6K1的表达增加,并与患者预后不良相关。p70S6K1特异抑制剂PF-4708671能降低细胞生长速率、诱导细胞衰老、促进细胞周期阻滞和减弱细胞迁移能力。此外,蟾蜍灵可明显抑制CRC细胞生长,下调p70S6K1的表达。结论p70S6K1可能是蟾蜍灵的新靶点,其可作为CRC治疗的潜在靶点。

OBJECTIVE To explore the effects of p70S6K1 in colorectal cancer(CRC)and its association with bufalin.METHODS In this study,the change of p70S6K1 expression in CRC tissues was detected by immunohistochemistry,and the correlation between p70S6K1 and CRC patient outcomes was evaluated.Furthermore,the effects of PF-4708671 on cell growth,cellular senescence,cell cycle and cell migration of CRC were determined by MTT assay,β-galactosidase staining,cell cycle staining and wound-healing assay,respectively.In addition,the effects of bufalin on growth rate of CRC cells and p70S6K1 expression were assessed.RESULTS The expression of p70S6K1 was increased in CRC samples compared to normal controls,which was associated with poor prognosis.PF-4708671 treatment reduced cell growth rate,induced cellular senescence,arrested cell cycle and attenuated cell migration ability by inhibiting p70S6K1 expression.Bufalin could restrain cell growth distinctly by decreasing downregulate p70S6K1 expression.CONCLUSION These findings suggest that p70S6K1 may be a new target of bufalin,and can act as a potential therapeutic target for CRC treatment.