Evidence map›Paper›PMID 41078141›Full record

ArticleJournal of cellular and molecular medicine2025

Repurposing Doxycycline to Overcome High-Glucose-Induced Mitochondrial Biogenesis-Mediated Chemoresistance in Colorectal Cancer Cells.

Chang-Han Wu, Ching-Wen Huang, Yen-Cheng Chen, Kwan-Ling Yip, Zhi-Feng Miao, Wei-Chih Su, Tsung-Kun Chang, Hsiang-Lin Tsai, Yung-Sung Yeh, Hsiao-Sheng Liu and 1 more

Abstract read
In one paragraph

Article in Journal of cellular and molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
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

11 authors.

Chang-Han WuDivision of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ching-Wen HuangDivision of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yen-Cheng ChenDivision of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Kwan-Ling YipDivision of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Zhi-Feng MiaoDivision of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Wei-Chih SuDivision of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Tsung-Kun ChangDivision of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hsiang-Lin TsaiDivision of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yung-Sung YehDivision of Trauma and Surgical Critical Care, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hsiao-Sheng LiuMaster of Science Program in Tropical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Jaw-Yuan WangDivision of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.ORCID 0000-0002-7705-2621

Funding

National Science and Technology Council 109-2314-B-037-046-MY3National Science and Technology Council 111-2314-B-037-070-MY3
6 · The paper itself

Abstract

Chemoresistance is a major contributor to treatment failure in most patients with cancer. Hyperglycaemia enhances chemoresistance in stage III colorectal cancer (CRC) patients, potentially through a mechanism involving c-Myc. Phospho-PGC-1α (p-PGC-1α), a transcription coactivator, regulates energy metabolism with c-Myc and is a key regulator of mitochondrial biogenesis. We hypothesised that high glucose (HG) promotes mitochondrial biogenesis by upregulating c-Myc and p-PGC-1α, thus enhancing chemoresistance in CRC cells, and that inhibiting mitochondrial biogenesis alleviates this chemoresistance. In vitro, HG significantly increased mitochondrial mass (p < 0.001), oxygen consumption rate (p < 0.001), cell migration (p < 0.05) and oxaliplatin resistance (p < 0.001) in LoVo and HCT116 cells. p-PGC-1α and COX4 protein expression were increased in the HG and oxaliplatin-resistance groups in LoVo and HCT116 cells (all p < 0.001) and decreased in the doxycycline group (p < 0.001). In vivo, doxycycline combined with oxaliplatin more notably reduced tumour volume than oxaliplatin alone in hyperglycaemic BALB/c nude mice (p < 0.05). c-Myc, p-PGC-1α and COX4 protein expression were significantly higher in tissues with CRC and hyperglycaemia who experienced relapse than in those with CRC and normoglycaemia who did not experience relapse (all p < 0.05). Overall, this study demonstrated that HG upregulates p-PGC-1α and COX4 expression to enhance oxaliplatin resistance by promoting mitochondrial biogenesis and indicates that doxycycline can overcome the chemoresistance induced by HG. Repurposing of doxycycline might reduce chemoresistance in hyperglycaemic CRC patients receiving adjuvant chemotherapy.

Indexed as

Colorectal NeoplasmsDoxycyclineDrug RepositioningDrug Resistance, NeoplasmGlucoseMitochondriaOrganelle BiogenesisAnimalsCell Line, TumorCell MovementGene Expression Regulation, NeoplasticHCT116 CellsHumansMaleMiceMice, Inbred BALB CDoxycyclineGlucoseOxaliplatinPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPPARGC1A protein, humanProto-Oncogene Proteins c-mycchemoresistancedoxycycline repurposehyperglycaemiamitochondrial biogenesisp‐PGC‐1α overexpression

Identifiers

PMID41078141
PMCPMC12516229

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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.