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Study · Animal study (in vivo) · mouse · 2019

4 results

Inhibition of activin-like kinase 4/5 attenuates cancer cachexia associated muscle wasting.

Levolger S, Wiemer EAC, van Vugt JLA, Huisman SA, van Vledder MG, van Damme-van Engel S, Ambagtsheer G, IJzermans JNM, de Bruin RWF

Scientific reports8 Jul 2019Cited by 14 (Europe PMC)

PMID31285507 (opens in a new tab)PMCIDPMC6614551 (opens in a new tab)DOI10.1038/s41598-019-46178-9 (opens in a new tab)PepBankPUB-31285507
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Summary

Cancer mediated activation of the ActRIIB-ALK4/5 heterodimer by myostatin is strongly associated with muscle wasting. We investigated in vitro and in vivo the efficacy of ALK4/5 receptor blockers SB431542 and GW788388 in preventing muscle wasting, and explored synergy with IGF-I analogue LONG R3 (LR3) IGF-I. In vitro, C2C12 skeletal muscle cells were treated with vehicle, SB431542, GW788388 and LR3 IGF-I. A C26-CD2F1 cachexia model was used to induce cachexia in vivo. Mice were allocated as non-tumour bearing (NTB) or C26 tumour-bearing (C26 TB) vehicle control, treated with SB431542, LR3 IGF-I, SB431542 and LR3 IGF-I, or GW788388 (intraperitoneally or orally). In vitro, differentiation index and mean nuclei count increased using SB431542, GW788388, LR3 IGF-I. In vivo, GW788388 was superior to SB431542 in limiting loss of bodyweight, grip-strength and gastrocnemius weight. and downregulated Atrogin-1 expression comparable to NTB mice. LR3 IGF-I treatment limited loss of muscle mass, but at the expense of accelerated tumour growth. In conclusion, treatment with GW788388 prevented cancer cachexia, and downregulated associated ubiquitin ligase Atrogin-1.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In mice with C26 tumours, LR3 IGF-I treatment limited loss of muscle mass.

    In plain wordsIn mice with cancer cachexia, LR3 IGF-I limited muscle loss compared with vehicle.

    Peptide
    IGF-1 LR3
    Outcome
    DecreaseLoss of muscle mass
    Study

    mousen: not reported in source

    C26 tumour-bearing CD2F1 cachexia model
    Comparator
    Vehicle
    Outcome group
    Muscle injury and repair · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    LR3 IGF-I treatment limited loss of muscle mass, but at the expense of accelerated tumour growth.
    2 context sentences
    Summary · context
    A C26-CD2F1 cachexia model was used to induce cachexia in vivo.
    Summary · context
    Mice were allocated as non-tumour bearing (NTB) or C26 tumour-bearing (C26 TB) vehicle control, treated with SB431542, LR3 IGF-I, SB431542 and LR3 IGF-I, or GW788388 (intraperitoneally or orally).
  2. 02AnimalAnimal study (in vivo)Safety outcome

    In mice with C26 tumours, LR3 IGF-I treatment accelerated tumour growth.

    In plain wordsIn mice with cancer cachexia, LR3 IGF-I sped up tumour growth compared with vehicle.

    Peptide
    IGF-1 LR3
    Outcome
    IncreaseTumour growth
    Study

    mousen: not reported in source

    C26 tumour-bearing CD2F1 cachexia model
    Comparator
    Vehicle
    Outcome group
    Tumor growth · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    LR3 IGF-I treatment limited loss of muscle mass, but at the expense of accelerated tumour growth.
    2 context sentences
    Summary · context
    A C26-CD2F1 cachexia model was used to induce cachexia in vivo.
    Summary · context
    Mice were allocated as non-tumour bearing (NTB) or C26 tumour-bearing (C26 TB) vehicle control, treated with SB431542, LR3 IGF-I, SB431542 and LR3 IGF-I, or GW788388 (intraperitoneally or orally).
  3. 03LabIn vitro (cells)Efficacy outcome

    In C2C12 skeletal muscle cells, LR3 IGF-I increased the differentiation index.

    In plain wordsIn muscle cells in a dish, LR3 IGF-I increased how far the cells matured.

    Peptide
    IGF-1 LR3
    Outcome
    IncreaseMyotube differentiation index
    Study

    n: not reported in source

    C2C12 skeletal muscle cells
    Comparator
    Vehicle
    Outcome group
    Muscle injury and repair · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In vitro, differentiation index and mean nuclei count increased using SB431542, GW788388, LR3 IGF-I.
    1 context sentence
    Summary · context
    In vitro, C2C12 skeletal muscle cells were treated with vehicle, SB431542, GW788388 and LR3 IGF-I.
  4. 04LabIn vitro (cells)Efficacy outcome

    In C2C12 skeletal muscle cells, LR3 IGF-I increased the mean nuclei count.

    In plain wordsIn muscle cells in a dish, LR3 IGF-I increased the mean number of nuclei per cell.

    Peptide
    IGF-1 LR3
    Outcome
    IncreaseMean nuclei count
    Study

    n: not reported in source

    C2C12 skeletal muscle cells
    Comparator
    Vehicle
    Outcome group
    Muscle injury and repair · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In vitro, differentiation index and mean nuclei count increased using SB431542, GW788388, LR3 IGF-I.
    1 context sentence
    Summary · context
    In vitro, C2C12 skeletal muscle cells were treated with vehicle, SB431542, GW788388 and LR3 IGF-I.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    13 Oct 2026, 21:44 UTC

    Study results updated

  2. Version 1

    13 Oct 2026, 16:31 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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