Evidence map›Paper›PMID 27278525›Full record

ArticleOncology reports2016

Fluoxetine synergizes with temozolomide to induce the CHOP-dependent endoplasmic reticulum stress-related apoptosis pathway in glioma cells.

Jian Ma, Yan-Ru Yang, Wei Chen, Mei-Hua Chen, Hao Wang, Xiao-Dan Wang, Li-Li Sun, Feng-Ze Wang, De-Cai Wang

Open access · hybridAbstract read
In one paragraph

Article in Oncology reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.7field-weighted citation impact, top 11% 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

35 citing papers in PubMed, 67 citations in OpenAlex.

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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

9 authors at 1 institution in 1 country.

Jian MaSchool of Pharmaceutical Science, Taishan Medical University, Taian, Shandong 271016, P.R. China.
Yan-Ru YangSchool of Pharmaceutical Science, Taishan Medical University, Taian, Shandong 271016, P.R. China.
Wei ChenSchool of Pharmaceutical Science, Taishan Medical University, Taian, Shandong 271016, P.R. China.
Mei-Hua ChenSchool of Pharmaceutical Science, Taishan Medical University, Taian, Shandong 271016, P.R. China.
Hao WangSchool of Pharmaceutical Science, Taishan Medical University, Taian, Shandong 271016, P.R. China.
Xiao-Dan WangSchool of Pharmaceutical Science, Taishan Medical University, Taian, Shandong 271016, P.R. China.
Li-Li SunSchool of Pharmaceutical Science, Taishan Medical University, Taian, Shandong 271016, P.R. China.
Feng-Ze WangSchool of Life Science, Taishan Medical University, Taian, Shandong 271016, P.R. China.
De-Cai WangSchool of Pharmaceutical Science, Taishan Medical University, Taian, Shandong 271016, P.R. China.
Taishan Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although temozolomide (TMZ) is the most effective chemotherapy agent for glioma, chemotherapy resistance has limited its clinical use. Fluoxetine (FLT), which is widely used in cancer-related depression, has exhibited potent anticancer properties in different cancer cell types. The aim of this study was i) to evaluate the antitumor mechanism of FLT, and ii) to further evaluate the effects of a combination of FLT and TMZ on glioma cells. Glioma cell lines were exposed to FLT and/or TMZ. Cell viability and apoptosis were examined by CCK-8 assay, flow cytometry and caspase-3 activity assay, respectively. The expression of endoplasmic reticulum-stress (ERS) apoptosis-related proteins was measured using real-time PCR and western blotting. Synergism between the two drugs was evaluated by the combination index (CI) through CompuSyn software. FLT significantly and dose-dependently inhibited the proliferation of various glioma cell lines, and rat glioma C6 cells had a highly sensitive response to the addition of FLT. FLT treatment increased the early apoptosis rate, induced typical apoptotic morphology in the C6 cells and activated caspase-3 with no change in the mitochondrial membrane potential. Further study showed that FLT activated the ERS marker, CHOP. This induction was associated with activation of the PERK-eIF2α-ATF4 and ATF6 cascade. Concomitantly, GADD34, a downstream molecule of CHOP, was also increased. Combined FLT and TMZ treatment showed a synergistic cytotoxic effect in the C6 glioma cells. Knockdown of CHOP expression abolished the synergistic effect of FLT and TMZ in the C6 cells, which suggests that FLT may sensitize glioma cells to TMZ through activation of the CHOP-dependent apoptosis pathway. These results revealed that FLT induced glioma cell apoptosis and sensitized glioma cells to TMZ through activation of the CHOP‑dependent apoptosis pathway. The present study provides a primary basis for using the combination of these drugs in patients with advanced glioma.

Indexed as

AnimalsAntineoplastic AgentsApoptosisBrain NeoplasmsCaspase 3Cell Line, TumorCell ProliferationDacarbazineDrug SynergismEndoplasmic Reticulum StressFluoxetineGliomaMembrane Potential, MitochondrialRatsSignal TransductionTemozolomideAntineoplastic AgentsCaspase 3DacarbazineDdit3 protein, ratFluoxetineTemozolomideTranscription Factor CHOP

Identifiers

PMID27278525
PMCPMC4933544
OpenAlexW2409471287

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.