Evidence map›Paper›PMID 41597239›Full record

ArticleCells2026

The Synergistic Effects of rhArg with Bcl-2 Inhibitors or Metformin Co-Treatment in Multiple Cancer Cell Models.

Lai-Pan Sze, Vicky Mei-Ki Ho, Wing-Ki Fung, Kin-Ho Law, Yifan Tu, Yik-Hing So, Sai-Fung Chung, Wing-Leung Wong, Zhen Liu, Alisa Sau-Wun Shum and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cells, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Lai-Pan SzeDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Vicky Mei-Ki HoDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Wing-Ki FungDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Kin-Ho LawDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Yifan TuDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Yik-Hing SoDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Sai-Fung ChungDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Wing-Leung WongDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.ORCID 0000-0001-7191-7578
Zhen LiuState Key Laboratory of Marine Food Processing and Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao 266404, China.
Alisa Sau-Wun ShumSchool of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Leo Man-Yuen LeeDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.ORCID 0000-0002-2089-9311
Yun-Chung LeungDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.ORCID 0000-0003-3590-7027

Funding

Hong Kong Research Grant Council (RGC), General Research Fund B-Q89F, 15307021Lo Ka Chung Charitable Foundation 847EPolyU Programme R-ZH4GState Key Laboratory of Chemical Biology and Drug Discovery KBBX4
6 · The paper itself

Abstract

backgroundRecombinant human arginase (rhArg) has been proven to exhibit an anticancer effect via arginine starvation. To further improve the efficacy of rhArg, we examined the feasibility of a combination strategy with Bcl-2 inhibitors (ABT263 and ABT199) or an antidiabetic drug (metformin) and investigated the mechanistic basis for these strategies.

methodsThe combination effects were evaluated in a panel of human cancer cell lines modeling pancreatic ductal carcinoma (PDAC), triple-negative breast cancer (TNBC), colorectal cancer (CRC) and glioblastoma (GBM). Western blot analysis was used to evaluate the expression of apoptotic and cell cycle markers. MTT assay was used to evaluate the combination efficacy. Flow cytometric assays were used to investigate the apoptotic and cell cycle effects.

resultsThe combination of rhArg with sublethal doses of ABT263 significantly induced dose-dependent apoptosis, with elevated expression of apoptotic markers and a CI of 0.47 in U251. The combination inhibited CDK2 and cyclin A expression, indicating that the observed synergy also resulted from cell cycle arrest. We also found that rhArg + metformin was synergistic in a time-dependent manner. Compared to other amino acid depletion agents, rhArg + ABT263 was the most favorable combination pair.

conclusionsThe combination of rhArg and ABT263 enhanced apoptosis and cell cycle arrest, demonstrating a potential broad-spectrum antitumor strategy.

Indexed as

ArginaseMetforminNeoplasmsProto-Oncogene Proteins c-bcl-2Aniline CompoundsApoptosisCell CycleCell Line, TumorCell ProliferationDrug SynergismHumansRecombinant ProteinsSulfonamidesAniline CompoundsArginaseMetforminnavitoclaxProto-Oncogene Proteins c-bcl-2Recombinant ProteinsSulfonamidesABT263anticancerBcl-2 inhibitordrug combinationmetforminrecombinant human arginase (rhArg)

Identifiers

PMID41597239
PMCPMC12839320

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.