Suppression of PC-1/PrLZ sensitizes prostate cancer cells to ionizing radiation by attenuating DNA damage repair and inducing autophagic cell death

Zeng Fu Shang, Qiang Wei, Lan Yu, Fang Huang, Bei Bei Xiao, Hongtao Wang, Man Song, Li Wang, Jianguang Zhou, Jian Wang, Shanhu Li

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Radiotherapy is promising and effective for treating prostate cancer but the addition of a tumor cell radiosensitizer would improve therapeutic outcomes. PC-1/ PrLZ, a TPD52 protein family member is frequently upregulated in advanced prostate cancer cells and may be a biomarker of aggressive prostate cancer. Therefore, we investigated the potential role of PC-1/PrLZ for increasing radioresistance in human prostate cancer cell lines. Growth curves and survival assays after g-ray irradiation confirmed that depletion of endogenous PC-1/PrLZ significantly increased prostate cancer cell radiosensitivity. Irradiation (IR) increased PC-1/PrLZ expression in a doseand time-dependent manner and increased radiosensitivity in PC-1/PrLZ-suppressed cells was partially due to decreased DNA double strand break (DBS) repair which was measured with comet and gH2AX foci assays. Furthermore, depletion of PC-1/PrLZ impaired the IR-induced G2/M checkpoint, which has been reported to be correlate with radioresistance in cancer cells. PC-1/PrLZ-deficient cells exhibited higher level of autophagy when compared with control cells. Thus, specific inhibition of PC-1/PrLZ might provide a novel therapeutic strategy for radiosensitizing prostate cancer cells.

Original languageEnglish (US)
Pages (from-to)62340-62351
Number of pages12
JournalOncotarget
Volume7
Issue number38
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Keywords

  • Autophage
  • PC-1/PrLZ
  • PCa
  • Radiotherapy

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Shang, Z. F., Wei, Q., Yu, L., Huang, F., Xiao, B. B., Wang, H., Song, M., Wang, L., Zhou, J., Wang, J., & Li, S. (2016). Suppression of PC-1/PrLZ sensitizes prostate cancer cells to ionizing radiation by attenuating DNA damage repair and inducing autophagic cell death. Oncotarget, 7(38), 62340-62351. https://doi.org/10.18632/oncotarget.11470