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


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 dose- and 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.

SUBMITTER: Shang ZF 

PROVIDER: S-EPMC5308731 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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

Shang Zeng-Fu ZF   Wei Qiang Q   Yu Lan L   Huang Fang F   Xiao Bei-Bei BB   Wang Hongtao H   Song Man M   Wang Li L   Zhou Jianguang J   Wang Jian J   Li Shanhu S  

Oncotarget 20160901 38


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 confir  ...[more]

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