Suppression of PC-1/PrLZ sensitizes prostate cancer cells to ionizing radiation by attenuating DNA damage repair and inducing autophagic cell death.
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.
School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu 215123, China.
Zeng-Fu
ZF
Shang
Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Qiang
Q
Wei
Laboratory of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, China.
Lan
L
Yu
Laboratory of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, China.
Fang
F
Huang
School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu 215123, China.
Bei-Bei
BB
Xiao
Laboratory of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, China.
Hongtao
H
Wang
School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu 215123, China.
Man
M
Song
Laboratory of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, China.
Li
L
Wang
Laboratory of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, China.
Jianguang
J
Zhou
Laboratory of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, China.
Jian
J
Wang
Laboratory of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, China.
Shanhu
S
Li
D001343:Autophagy / Q000528:radiation effects*; D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004260:DNA Repair / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D059565:G2 Phase Cell Cycle Checkpoints / Q000528:radiation effects; D005720:Gamma Rays; D006657:Histones / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D010766:Phosphorylation; D011467:Prostate / Q000166:cytology / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011836:Radiation Tolerance; D015854:Up-Regulation
C468783:H2AX protein, human; D006657:Histones; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C114751:TPD52 protein, human
PC-1/PrLZ; PCa; autophage; radiotherapy
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