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Inhibition of heme oxygenase-1 enhances the chemosensitivity of laryngeal squamous cell cancer Hep-2 cells to cisplatin

Abstract

It has been previously reported that cisplatin is a well-known anticancer drug being used against a wide range of malignancies including head and neck, ovarian and non-small cell lung carcinoma, and demonstrated its anticancer activity by reacting with DNA or changing cell structure, immune response, reactive oxygen species level (ROS). In this research we proved that cisplatin induced cell injuries and heme oxygenase-1 (HO-1) expression in laryngeal squamous cell cancer Hep-2 cells through ROS generation. The induction of HO-1 clearly protected Hep-2 cells from cisplatin-induced cell death and ROS reaction, and the inhibitor of HO-1 enhanced the cell death and ROS generation induced by cisplatin. Furthermore, the HO-1 expression induced by cisplatin was strongly inhibited by the knockdown of nuclear factor-erythroid-2-related factor-2 (Nrf-2), and the oxidative damages induced by cisplatin were significantly enhanced. Therefore, it may be concluded that the inhibition of HO-1 or the knockdown of Nrf-2 significantly enhanced cisplatin’s anticancer effects on Hep-2 cells. In clinic, with the overexpression of HO-1 in laryngeal squamous cancer tissues, the combination of cisplatin with the inhibitor of HO-1 or Nrf-2 siRNA may act as a new method to the treatment of laryngeal squamous cancer.

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Abbreviations

ARE:

Antioxidant response element

DCFH-DA:

Dichlorofluorescin diacetate

HO-1:

Heme oxygenase-1

Nrf-2:

Nuclear factor-erythroid-2-related factor-2

PBS:

Phosphate-buffered saline

PI:

Propidium iodide

ROS:

Reactive oxygen species

ZnPPIX:

Zinc protoporphyrin IX

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Acknowledgments

This study was supported by Grants from Natural Science Foundation of Hebei province (H2013206264).

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Correspondence to Bao-shan Wang.

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Xin Lv and Dong-mei Song have contributed equally to this work.

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Lv, X., Song, Dm., Niu, Yh. et al. Inhibition of heme oxygenase-1 enhances the chemosensitivity of laryngeal squamous cell cancer Hep-2 cells to cisplatin. Apoptosis 21, 489–501 (2016). https://doi.org/10.1007/s10495-016-1216-7

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  • DOI: https://doi.org/10.1007/s10495-016-1216-7

Keywords

  • Cisplatin
  • Hep-2
  • HO-1
  • Nrf-2
  • Apoptosis