Inhibition of heat shock protein 27 phosphorylation promotes sensitivity to 5-fluorouracil in colorectal cancer cells
Inhibition of heat shock protein 27 phosphorylation promotes sensitivity to 5-fluorouracil in colorectal cancer cells
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DOI：
10.3892/ol.2014.2580
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发表时间：
2014-12-01
期刊：
影响因子：
2.9
通讯作者：
Kitagawa, Yuko
中科院分区：
文献类型：
--
作者：
Matsunaga, Atsushi;Ishii, Yoshiyuki;Kitagawa, Yuko
本研究的目的是探讨是否抑制HSP 27磷酸化，影响某些细胞功能，调节敏感性5-氟尿嘧啶（5-FU）在结直肠癌细胞。暴露于5-FU的HCT 116和HCT 15细胞表达高水平的HSP 27与低5-FU敏感性引起的HSP 27表达的变化很小，但诱导上调HSP 27磷酸化，特别是在Ser 78。相比之下，在表达低水平HSP 27且5-FU敏感性高的HT 29细胞中暴露于5-FU略微增加HSP 27表达，磷酸化最小。用选择性抑制剂p38丝裂原活化蛋白激酶（MAPK; SB 203580）处理，引起HSP 27磷酸化的剂量依赖性抑制，其被5-FU上调，降低了HCT 116和HCT 15细胞中5-FU的半数最大抑制浓度值。然而，用SB 203580处理对细胞生长或存活没有表现出显著影响。总之，本研究表明，通过p38 MAPK的选择性抑制剂抑制HSP 27磷酸化促进5-FU敏感性，而不引起结直肠癌细胞的细胞毒性。
The aim of the present study was to investigate whether the inhibition of HSP27 phosphorylation, which affects certain cellular functions, modulates sensitivity to 5-fluorouracil (5-FU) in colorectal cancer cells. Exposure to 5-FU in HCT116 and HCT15 cells expressing high levels of HSP27 with a low 5-FU sensitivity caused a minimal change in HSP27 expression, but induced the upregulation of HSP27 phosphorylation, particularly at Ser78. By contrast, exposure to 5-FU in HT29 cells expressing a low level of HSP27 with a high 5-FU sensitivity marginally increased HSP27 expression, with minimal phosphorylation. Treatment with a selective inhibitor, p38 mitogen-activated protein kinase (MAPK; SB203580), caused the dose-dependent suppression of HSP27 phosphorylation, which was upregulated by 5-FU, reducing the half maximal inhibitory concentration values of 5-FU in the HCT116 and HCT15 cells. However, treatment with SB203580 exhibited no significant effect on cell growth or survival. In conclusion, this study indicated that the inhibition of HSP27 phosphorylation by a selective inhibitor of p38 MAPK promotes 5-FU sensitivity without causing cytotoxicity in colorectal cancer cells.