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首页> 外文期刊>Cancer letters >The Hsp70 inhibiting peptide aptamer A17 potentiates radiosensitization of tumor cells by Hsp90 inhibition
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The Hsp70 inhibiting peptide aptamer A17 potentiates radiosensitization of tumor cells by Hsp90 inhibition

机译：HSP70抑制肽Aptamer A17通过Hsp90抑制增强了肿瘤细胞的放射敏化症

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The inhibition of heat shock protein 90 (Hsp90) is a promising strategy to increase the radiosensitivity of tumor cells. However, Hsp90 inhibition induces the expression of Hsp70 which is a prominent cytoprotective protein. Therefore, dual targeting of Hsp70 and Hsp90 might be beneficial to increase the radiosensitivity of tumor cells. Hsp70 inhibiting peptide aptamers have been shown to increase the sensitivity of tumor cells to apoptosis induced by different anticancer drugs. Herein, we studied the radiosensitizing activity of the Hsp70 inhibiting peptide aptamer A17 in combination with the Hsp90 inhibitor NVP-AUY922. Whereas A17 significantly increased apoptosis induction by NVP-AUY922 it did not significantly affect the radiosensitivity of human lung and breast cancer cells. However, Hsp70 inhibition by the aptamer A17 potentiated the radiosensitizing effects of the Hsp90 inhibitor NVP-AUY922. Mechanistically we speculate that an increased number of DNA double strand breaks and an enhanced G(2)/M arrest might be responsible for the increased radiosensitization in A17 expressing tumor cells. Therefore, the simultaneous inhibition of Hsp90 and Hsp70 combined with radiotherapy might provide a promising anti-cancer strategy. (C) 2017 Elsevier B.V. All rights reserved.
机译：热休克蛋白90（HSP90）的抑制是增加肿瘤细胞的放射敏感性的有希望的策略。然而，HSP90抑制诱导Hsp70的表达，其是突出的细胞保护蛋白。因此，HSP70和HSP90的双重靶向可能有益，可以增加肿瘤细胞的放射敏感性。已经显示HSP70抑制肽适体，以提高肿瘤细胞对由不同抗癌药物诱导的凋亡的敏感性。在此，我们研究了HSP70抑制肽Aptamer A17的放射敏化活性与HSP90抑制剂NVP-Auy922的组合。虽然A17明显增加了NVP-Auy922的凋亡诱导，但它没有显着影响人肺和乳腺癌细胞的放射敏感性。然而，HSP70通过适体A17抑制抑制性HSP90抑制剂NVP-Auy922的放射敏化效应。机械地，我们推测DNA双链断裂数量增加，增强的G（2）/ m被阻止可能是对表达肿瘤细胞的A17中的增加的放射敏化。因此，同时抑制HSP90和HSP70与放射疗法结合的可能提供有前途的抗癌策略。 （c）2017 Elsevier B.v.保留所有权利。

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