# AB-Flu nanodrug combined with exercise intervention enhances ROS-mediated antitumor effects in melanoma

**Authors:** Yuanbing Zhou, Jinke Ma, Ziyu Zhang, Xiaodan Niu, Huiyu Yan, Jun Zhang

PMC · DOI: 10.3389/fphys.2026.1767235 · Frontiers in Physiology · 2026-02-06

## TL;DR

Combining AB-Flu nanodrugs with exercise improves melanoma treatment by reducing tumor hypoxia and increasing cell death.

## Contribution

This study demonstrates a novel combination of nanodrugs and exercise to enhance melanoma therapy through ROS-mediated tumor cell apoptosis.

## Key findings

- Combination therapy achieved 56% tumor growth inhibition, significantly higher than monotherapies.
- Combination therapy reduced tumor hypoxia and increased tumor cell apoptosis.
- ROS levels were significantly elevated in the combination therapy group.

## Abstract

This study aims to investigate the synergistic effects of AB-Flu nanodrugs and exercise intervention on enhancing the antitumor effects in melanoma by improving the hypoxic tumor microenvironment (TME). The focus is on evaluating how this combination influences reactive oxygen species (ROS) levels, inhibition of melanoma in vivo.

An intact B16F10 melanoma mouse model was established, and mice were divided into four groups: control, AB-Flu treatment, exercise intervention, and combination therapy (AB-Flu + exercise). AB-Flu nanodrug was administered intraperitoneally, while exercise was facilitated by a weighted swimming intervention. Tumor growth, tumor hypoxia, ROS levels, and apoptosis were analyzed through tumor volume measurements, histological staining, and ROS detection assays. The antitumor effects of different treatments were compared.

The combination therapy group showed the most significant tumor inhibition efficacy with tumor growth inhibition rates of 56%, compared to 30% for the AB-Flu monotherapy group and 41% for the exercise group. Additionally, tumor tissues from the combination group exhibited significantly lower levels of hypoxia and enhanced tumor cell apoptosis. ROS levels were substantially higher in the combination therapy group compared to other groups, indicating that the combination of AB-Flu and exercise synergistically elevated ROS production, which may contribute to increased tumor cell apoptosis. No significant toxicity was observed in major organs.

The combination of AB-Flu nanodrugs and exercise intervention significantly enhances the antitumor effects in melanoma by improving the hypoxic TME, elevating ROS levels, and promoting apoptosis in tumor cells. This strategy may offer a potential approach for melanoma therapy.

## Linked entities

- **Diseases:** melanoma (MONDO:0005105)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** SPATA2 (spermatogenesis associated 2) [NCBI Gene 9825] {aka PD1, PPP1R145, tamo}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, CXCR3 (C-X-C motif chemokine receptor 3) [NCBI Gene 2833] {aka CD182, CD183, CKR-L2, CMKAR3, GPR9, IP10-R}, Il2ra (interleukin 2 receptor, alpha chain) [NCBI Gene 16184] {aka CD25, Il2r, Ly-43}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673] {aka B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1}, CXCL9 (C-X-C motif chemokine ligand 9) [NCBI Gene 4283] {aka CMK, Humig, MIG, SCYB9, crg-10}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, CCR2 (C-C motif chemokine receptor 2) [NCBI Gene 729230] {aka CC-CKR-2, CCR-2, CCR2A, CCR2B, CD192, CKR2}, CCR5 (C-C motif chemokine receptor 5) [NCBI Gene 1234] {aka CC-CKR-5, CCCKR5, CCR-5, CD195, CKR-5, CKR5}, Cd3e (CD3 antigen, epsilon polypeptide) [NCBI Gene 12501] {aka CD3, CD3epsilon, T3e}, Prdx6-ps2 (peroxiredoxin 6 pseudogene 2) [NCBI Gene 384001] {aka Aop2-rs2, GPx*, Prdx6-rs2}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, CXCL11 (C-X-C motif chemokine ligand 11) [NCBI Gene 6373] {aka H174, I-TAC, IP-9, IP9, SCYB11, SCYB9B}, Alb (albumin) [NCBI Gene 11657] {aka Alb-1, Alb1, BCL001, BCL002, BPL001}, Gpt (glutamic pyruvic transaminase, soluble) [NCBI Gene 76282] {aka 1300007J06Rik, 2310022B03Rik, ALT, ALT1, Gpt-1, Gpt1}, Slc17a5 (solute carrier family 17 (anion/sugar transporter), member 5) [NCBI Gene 235504] {aka 4631416G20Rik, 4732491M05, AST, ISSD, NSD, SD}
- **Diseases:** inflammation (MESH:D007249), PDAC (MESH:C537768), Melanoma (MESH:D008545), Cancer (MESH:D009369), skin cancer (MESH:D012878), hypoxic (MESH:D002534), fatigue (MESH:D005221), Hypoxia (MESH:D000860), metastasis (MESH:D009362), deaths (MESH:D003643), tumorigenic (MESH:D002471), cytotoxic (MESH:D064420), triple-negative breast cancer metastasis (MESH:D064726), breast cancer (MESH:D001943), organ damage (MESH:D000092124), damage to liver and kidney functions (MESH:D056486), lymphocytosis (MESH:D008218), necrosis (MESH:D009336), solid (MESH:D018250)
- **Chemicals:** paraffin (MESH:D010232), TCEP (MESH:C080938), oxygen (MESH:D010100), Lactate (MESH:D019344), EDTA (MESH:D004492), Adrenaline (MESH:D004837), vemurafenib (MESH:D000077484), phenazine methosulfate (MESH:D008773), AB-Flu (-), H2S (MESH:D006862), H&amp;E (MESH:D006371), Hematoxylin (MESH:D006416), nitroblue tetrazolium (MESH:D009580), MDA (MESH:D008315), fatty acid (MESH:D005227), Hypoxyprobe-1 (MESH:C033815), carbon dioxide (MESH:D002245), lipid (MESH:D008055), Fluvastatin (MESH:D000077340), PBS (MESH:D007854), NAD+ (MESH:D009243), PMS (MESH:D011399), eosin (MESH:D004801), DMSO (MESH:D004121), formalin (MESH:D005557), Crea (MESH:D003404), ROS (MESH:D017382), Z (MESH:C000597310)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Salmonella enterica subsp. enterica serovar Typhimurium (no rank) [taxon 90371], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** B16F10 — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_0159), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12920243/full.md

## References

61 references — full list in the complete paper: https://tomesphere.com/paper/PMC12920243/full.md

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Source: https://tomesphere.com/paper/PMC12920243