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Lamprou I, Tsolou A, Kakouratos C, et al. Suppressed PLIN3 frequently occurs in prostate cancer, promoting docetaxel resistance via intensified autophagy, an event reversed by chloroquine. Med Oncol. 2021;38(10):116doi: 10.1007/s12032-021-01566-y.
Lamprou, I., Tsolou, A., Kakouratos, C., Mitrakas, A. G., Xanthopoulou, E. T., Kassela, K., Karakasiliotis, I., Zois, C. E., Giatromanolaki, A., & Koukourakis, M. I. (2021). Suppressed PLIN3 frequently occurs in prostate cancer, promoting docetaxel resistance via intensified autophagy, an event reversed by chloroquine. Medical oncology (Northwood, London, England), 38(10), 116. https://doi.org/10.1007/s12032-021-01566-y
Lamprou, Ioannis, et al. "Suppressed PLIN3 frequently occurs in prostate cancer, promoting docetaxel resistance via intensified autophagy, an event reversed by chloroquine." Medical oncology (Northwood, London, England) vol. 38,10 (2021): 116. doi: https://doi.org/10.1007/s12032-021-01566-y
Lamprou I, Tsolou A, Kakouratos C, Mitrakas AG, Xanthopoulou ET, Kassela K, Karakasiliotis I, Zois CE, Giatromanolaki A, Koukourakis MI. Suppressed PLIN3 frequently occurs in prostate cancer, promoting docetaxel resistance via intensified autophagy, an event reversed by chloroquine. Med Oncol. 2021 Aug 19;38(10):116. doi: 10.1007/s12032-021-01566-y. PMID: 34410522; PMCID: PMC8374126.
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Med Oncol. 2021 Aug 19;38(10):116. doi: 10.1007/s12032-021-01566-y.

Suppressed PLIN3 frequently occurs in prostate cancer, promoting docetaxel resistance via intensified autophagy, an event reversed by chloroquine.

Medical oncology (Northwood, London, England)

Ioannis Lamprou, Avgi Tsolou, Christos Kakouratos, Achilleas G Mitrakas, Erasmia T Xanthopoulou, Katerina Kassela, Ioannis Karakasiliotis, Christos E Zois, Alexandra Giatromanolaki, Michael I Koukourakis

Affiliations

  1. Department of Radiotherapy/Oncology, Democritus University of Thrace, PO BOX 12, 68100, Alexandroupolis, Greece.
  2. Laboratory of Biology, Democritus University of Thrace, 68100, Alexandroupolis, Greece.
  3. Department of Pathology, Democritus University of Thrace, 68100, Alexandroupolis, Greece.
  4. Department of Radiotherapy/Oncology, Democritus University of Thrace, PO BOX 12, 68100, Alexandroupolis, Greece. [email protected].

PMID: 34410522 PMCID: PMC8374126 DOI: 10.1007/s12032-021-01566-y

Abstract

Lipid metabolism reprogramming is one of the adaptive events that drive tumor development and survival, and may account for resistance to chemotherapeutic drugs. Perilipins are structural proteins associated with lipophagy and lipid droplet integrity, and their overexpression is associated with tumor aggressiveness. Here, we sought to explore the role of lipid droplet-related protein perilipin-3 (PLIN3) in prostate cancer (PCa) chemotherapy. We investigated the role of PLIN3 suppression in docetaxel cytotoxic activity in PCa cell lines. Additional effects of PLIN3 depletion on autophagy-related proteins and gene expression patterns, apoptotic potential, proliferation rate, and ATP levels were examined. Depletion of PLIN3 resulted in docetaxel resistance, accompanied by enhanced autophagic flux. We further assessed the synergistic effect of autophagy suppression with chloroquine on docetaxel cytotoxicity. Inhibition of autophagy with chloroquine reversed chemoresistance of stably transfected shPLIN3 PCa cell lines, with no effect on the parental ones. The shPLIN3 cell lines also exhibited reduced Caspase-9 related apoptosis initiation. Moreover, we assessed PLIN3 expression in a series of PCa tissue specimens, were complete or partial loss of PLIN3 expression was frequently noted in 70% of the evaluated specimens. Following PLIN3 silencing, PCa cells were characterized by impaired lipophagy and acquired an enhanced autophagic response upon docetaxel-induced cytotoxic stress. Such an adaptation leads to resistance to docetaxel, which could be reversed by the autophagy blocker chloroquine. Given the frequent loss of PLIN3 expression in PCa specimens, we suggest that combination of docetaxel with chloroquine may improve the efficacy of docetaxel treatment in PLIN3-deficient cancer patients.

© 2021. Springer Science+Business Media, LLC, part of Springer Nature.

Keywords: Autophagy (Lipophagy); Chemoresistance; Chloroquine; Docetaxel; Perilipins; Prostate cancer

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