Evidence map›Paper›PMID 25275598›Full record

ArticleCell death & disease2014

PI3K/Akt/mTOR pathway inhibitors enhance radiosensitivity in radioresistant prostate cancer cells through inducing apoptosis, reducing autophagy, suppressing NHEJ and HR repair pathways.

L Chang, P H Graham, J Hao, J Ni, J Bucci, P J Cozzi, J H Kearsley, Y Li

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 195 papers.

0numbers the graph read from it
0cells of the map it votes in
195citing papers in PubMed
11.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

195 citing papers in PubMed, 309 citations in OpenAlex.

  1. Review
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  5. Variable cellular and radiobiological effects of [Journal of experimental & clinical cancer research : CR · 2026
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  10. Radiosensitizers in Cancer Therapy: A Global Bibliometric Analysis.bioRxiv : the preprint server for biology · 2025
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135 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 1 country.

L Chang1] Cancer Care Centre and Prostate Cancer Institute, St. George Hospital, SESLHD, Kogarah, New South Wales 2217, Australia [2] Faculty of Medicine, St. George and Sutherland Clinical School, University of New South Wales, Kensington, New South Wales 2052, Australia.
P H Graham1] Cancer Care Centre and Prostate Cancer Institute, St. George Hospital, SESLHD, Kogarah, New South Wales 2217, Australia [2] Faculty of Medicine, St. George and Sutherland Clinical School, University of New South Wales, Kensington, New South Wales 2052, Australia.
J Hao1] Cancer Care Centre and Prostate Cancer Institute, St. George Hospital, SESLHD, Kogarah, New South Wales 2217, Australia [2] Faculty of Medicine, St. George and Sutherland Clinical School, University of New South Wales, Kensington, New South Wales 2052, Australia.
J Ni1] Cancer Care Centre and Prostate Cancer Institute, St. George Hospital, SESLHD, Kogarah, New South Wales 2217, Australia [2] Faculty of Medicine, St. George and Sutherland Clinical School, University of New South Wales, Kensington, New South Wales 2052, Australia.
J Bucci1] Cancer Care Centre and Prostate Cancer Institute, St. George Hospital, SESLHD, Kogarah, New South Wales 2217, Australia [2] Faculty of Medicine, St. George and Sutherland Clinical School, University of New South Wales, Kensington, New South Wales 2052, Australia.
P J Cozzi1] Faculty of Medicine, St. George and Sutherland Clinical School, University of New South Wales, Kensington, New South Wales 2052, Australia [2] Department of Surgery, St. George Hospital, Kogarah, New South Wales 2217, Australia.
J H Kearsley1] Cancer Care Centre and Prostate Cancer Institute, St. George Hospital, SESLHD, Kogarah, New South Wales 2217, Australia [2] Faculty of Medicine, St. George and Sutherland Clinical School, University of New South Wales, Kensington, New South Wales 2052, Australia.
Y Li1] Cancer Care Centre and Prostate Cancer Institute, St. George Hospital, SESLHD, Kogarah, New South Wales 2217, Australia [2] Faculty of Medicine, St. George and Sutherland Clinical School, University of New South Wales, Kensington, New South Wales 2052, Australia.
St George Hospital · AUSutherland Hospital · AUSouth Eastern Sydney Local Health District · AUUNSW Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The PI3K/Akt/mTOR pathway has a central role in cancer metastasis and radiotherapy. To develop effective therapeutics to improve radiosensitivity, understanding the possible pathways of radioresistance involved and the effects of a combination of the PI3K/Akt/mTOR inhibitors with radiotherapy on prostate cancer (CaP) radioresistant cells is needed. We found that compared with parent CaP cells, CaP-radioresistant cells demonstrated G0/G1 and S phase arrest, activation of cell cycle check point, autophagy and DNA repair pathway proteins, and inactivation of apoptotic proteins. We also demonstrated that compared with combination of single PI3K or mTOR inhibitors (BKM120 or Rapamycin) and radiation, low-dose of dual PI3K/mTOR inhibitors (BEZ235 or PI103) combined with radiation greatly improved treatment efficacy by repressing colony formation, inducing more apoptosis, leading to the arrest of the G2/M phase, increased double-strand break levels and less inactivation of cell cycle check point, autophagy and non-homologous end joining (NHEJ)/homologous recombination (HR) repair pathway proteins in CaP-radioresistant cells. This study describes the possible pathways associated with CaP radioresistance and demonstrates the putative mechanisms of the radiosensitization effect in CaP-resistant cells in the combination treatment. The findings from this study suggest that the combination of dual PI3K/Akt/mTOR inhibitors (BEZ235 or PI103) with radiotherapy is a promising modality for the treatment of CaP to overcome radioresistance.

Indexed as

AutophagyDNA End-Joining RepairHomologous RecombinationPhosphoinositide-3 Kinase InhibitorsApoptosisCell CycleCell Line, TumorEnzyme InhibitorsHumansMalePhosphatidylinositol 3-KinasesProstatic NeoplasmsProto-Oncogene Proteins c-aktRadiation ToleranceSignal TransductionTOR Serine-Threonine KinasesEnzyme InhibitorsMTOR protein, humanPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-aktTOR Serine-Threonine Kinases

Identifiers

PMID25275598
PMCPMC4237243
OpenAlexW1969043065

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.