HSPB1 deficiency sensitizes melanoma cells to hyperthermia induced cell death.
HSPB1 deficiency sensitizes melanoma cells to hyperthermia induced cell death.
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DOI：
10.18632/oncotarget.11894
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发表时间：
2016-10-11
期刊：
影响因子：
--
通讯作者：
Gao XH
中科院分区：
文献类型：
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作者：
Wang HX;Yang Y;Guo H;Hou DD;Zheng S;Hong YX;Cai YF;Huo W;Qi RQ;Zhang L;Chen HD;Gao XH
在癌症治疗中，热疗已显示出作为单一药物或辅助其他疗法的临床效力。然而，由热休克蛋白等热敏基因诱导的耐热性会限制高温治疗的效果。在本研究中，我们发现HSPB1 （HSP27）在小鼠和人类黑色素瘤细胞系中都是热诱导或内源性高表达的。我们使用siRNA策略来降低HSPB1水平，并通过降低细胞活力和/或细胞增殖来增加对高温的不耐受。在潜在机制的研究中，我们发现与单独使用任何一种药物相比，HSPB1的下调进一步增加了高温处理黑色素瘤细胞中凋亡细胞的比例，并且两种药物都导致细胞周期阻滞在G0/G1或G2/M期。我们得出结论，热疗联合HSPB1沉默会增加细胞死亡，导致黑色素瘤细胞系生长失败，这意味着热疗联合HSPB1抑制在癌症治疗中的潜在临床应用。
Hyperthermia has shown clinical potency as a single agent or as adjuvant to other therapies in cancer treatment. However, thermotolerance induced by thermosensitive genes such as the heat shock proteins can limit the efficacy of hyperthermic treatment. In the present study, we identified HSPB1 (HSP27) is hyperthermically inducible or endogenously highly expressed in both murine and human melanoma cell lines. We used a siRNA strategy to reduce HSPB1 levels and showed increased intolerance to hyperthermia via reduced cell viability and/or proliferation of cells. In the investigation of underlying mechanisms, we found knock down of HSPB1 further increased the proportion of apoptotic cells in hyperthermic treated melanoma cells when compared with either single agent alone, and both agents leaded to cell cycle arrest at G0/G1 or G2/M phases. We concluded that hyperthermia combined with silencing of HSPB1 enhanced cell death and resulted in failure to thrive in melanoma cell lines, implying the potential clinical utility of hyperthermia in combination with HSPB1 inhibition in cancer treatment.