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Study · Animal study (in vivo) · mouse · 2015

7 results

Pharmacological targeting of the protein synthesis mTOR/4E-BP1 pathway in cancer-associated fibroblasts abrogates pancreatic tumour chemoresistance.

Duluc C, Moatassim-Billah S, Chalabi-Dchar M, Perraud A, Samain R, Breibach F, Gayral M, Cordelier P, Delisle MB, Bousquet-Dubouch MP, Tomasini R, Schmid H and 4 more

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Mathonnet M, Pyronnet S, Martineau Y, Bousquet C

EMBO molecular medicine1 Jun 2015Cited by 182 (Europe PMC)

PMID25834145 (opens in a new tab)PMCIDPMC4459815 (opens in a new tab)DOI10.15252/emmm.201404346 (opens in a new tab)PepBankPUB-25834145
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Summary

Pancreatic ductal adenocarcinoma (PDAC) is extremely stroma-rich. Cancer-associated fibroblasts (CAFs) secrete proteins that activate survival and promote chemoresistance of cancer cells. Our results demonstrate that CAF secretome-triggered chemoresistance is abolished upon inhibition of the protein synthesis mTOR/4E-BP1 regulatory pathway which we found highly activated in primary cultures of α-SMA-positive CAFs, isolated from human PDAC resections. CAFs selectively express the sst1 somatostatin receptor. The SOM230 analogue (Pasireotide) activates the sst1 receptor and inhibits the mTOR/4E-BP1 pathway and the resultant synthesis of secreted proteins including IL-6. Consequently, tumour growth and chemoresistance in nude mice xenografted with pancreatic cancer cells and CAFs, or with pieces of resected human PDACs, are reduced when chemotherapy (gemcitabine) is combined with SOM230 treatment. While gemcitabine alone has marginal effects, SOM230 is permissive to gemcitabine-induced cancer cell apoptosis and acts as an antifibrotic agent. We propose that selective inhibition of CAF protein synthesis with sst1-directed pharmacological compounds represents an anti-stromal-targeted therapy with promising chemosensitization potential.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In pancreatic cancer xenograft mice, adding pasireotide to gemcitabine reduced tumour growth versus gemcitabine alone.

    In plain wordsIn mice with pancreatic cancer grafts, pasireotide plus gemcitabine reduced tumour growth compared with gemcitabine alone.

    Peptide
    Pasireotide
    Outcome
    DecreaseTumour growth with gemcitabine
    Study

    mousen: not reported in source

    Nude mice bearing pancreatic cancer cells and CAFs or human PDAC xenografts
    Comparator
    Gemcitabine alone
    Outcome group
    Tumor growth · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Consequently, tumour growth and chemoresistance in nude mice xenografted with pancreatic cancer cells and CAFs, or with pieces of resected human PDACs, are reduced when chemotherapy (gemcitabine) is combined with SOM230 treatment. While gemcitabine alone has marginal effects, SOM230 is permissive to gemcitabine-induced cancer cell apoptosis and acts as an antifibrotic agent.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In pancreatic cancer xenograft mice, adding pasireotide to gemcitabine reduced chemoresistance versus gemcitabine alone.

    In plain wordsIn mice with pancreatic cancer grafts, pasireotide plus gemcitabine reduced chemotherapy resistance compared with gemcitabine alone.

    Peptide
    Pasireotide
    Outcome
    DecreaseChemoresistance with gemcitabine
    Study

    mousen: not reported in source

    Nude mice bearing pancreatic cancer xenografts
    Comparator
    Gemcitabine alone
    Outcome group
    Tumor growth · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Consequently, tumour growth and chemoresistance in nude mice xenografted with pancreatic cancer cells and CAFs, or with pieces of resected human PDACs, are reduced when chemotherapy (gemcitabine) is combined with SOM230 treatment. While gemcitabine alone has marginal effects, SOM230 is permissive to gemcitabine-induced cancer cell apoptosis and acts as an antifibrotic agent.
  3. 03AnimalAnimal study (in vivo)Mechanism

    In pancreatic cancer xenograft mice, pasireotide enabled gemcitabine-induced cancer cell apoptosis compared with gemcitabine alone.

    In plain wordsIn mice with pancreatic cancer grafts, pasireotide plus gemcitabine enabled cancer cell death compared with gemcitabine alone.

    Peptide
    Pasireotide
    Outcome
    IncreaseGemcitabine-induced cancer cell apoptosis
    Study

    mousen: not reported in source

    Pancreatic cancer xenografts
    Comparator
    Gemcitabine alone
    Outcome group
    Receptor activity and mechanism · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    While gemcitabine alone has marginal effects, SOM230 is permissive to gemcitabine-induced cancer cell apoptosis and acts as an antifibrotic agent.
    1 context sentence
    Summary · context
    Consequently, tumour growth and chemoresistance in nude mice xenografted with pancreatic cancer cells and CAFs, or with pieces of resected human PDACs, are reduced when chemotherapy (gemcitabine) is combined with SOM230 treatment.
  4. 04AnimalAnimal study (in vivo)Mechanism

    In pancreatic cancer xenograft mice, pasireotide acted as an antifibrotic agent.

    In plain wordsIn mice with pancreatic cancer grafts, pasireotide acted against fibrosis.

    Peptide
    Pasireotide
    Outcome
    DecreaseFibrosis
    Study

    mousen: not reported in source

    Pancreatic cancer xenografts
    Outcome group
    Receptor activity and mechanism · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    While gemcitabine alone has marginal effects, SOM230 is permissive to gemcitabine-induced cancer cell apoptosis and acts as an antifibrotic agent.
    1 context sentence
    Summary · context
    Consequently, tumour growth and chemoresistance in nude mice xenografted with pancreatic cancer cells and CAFs, or with pieces of resected human PDACs, are reduced when chemotherapy (gemcitabine) is combined with SOM230 treatment.
  5. 05LabIn vitro (cells)Mechanism

    In human pancreatic cancer-associated fibroblasts, pasireotide activated the sst1 receptor.

    In plain wordsIn cells from human pancreatic cancers, pasireotide activated the sst1 receptor.

    Peptide
    Pasireotide
    Outcome
    Increasesst1 receptor activation
    Study

    humann: not reported in source

    Primary cancer-associated fibroblasts from pancreatic ductal adenocarcinoma
    Outcome group
    Receptor activity and mechanism · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The SOM230 analogue (Pasireotide) activates the sst1 receptor and inhibits the mTOR/4E-BP1 pathway and the resultant synthesis of secreted proteins including IL-6.
    1 context sentence
    Summary · context
    Our results demonstrate that CAF secretome-triggered chemoresistance is abolished upon inhibition of the protein synthesis mTOR/4E-BP1 regulatory pathway which we found highly activated in primary cultures of α-SMA-positive CAFs, isolated from human PDAC resections.
  6. 06LabIn vitro (cells)Mechanism

    In human pancreatic cancer-associated fibroblasts, pasireotide inhibited the mTOR/4E-BP1 pathway.

    In plain wordsIn cells from human pancreatic cancers, pasireotide inhibited the mTOR/4E-BP1 pathway.

    Peptide
    Pasireotide
    Outcome
    DecreasemTOR/4E-BP1 pathway
    Study

    humann: not reported in source

    Primary cancer-associated fibroblasts from pancreatic ductal adenocarcinoma
    Outcome group
    Receptor activity and mechanism · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The SOM230 analogue (Pasireotide) activates the sst1 receptor and inhibits the mTOR/4E-BP1 pathway and the resultant synthesis of secreted proteins including IL-6.
    1 context sentence
    Summary · context
    Our results demonstrate that CAF secretome-triggered chemoresistance is abolished upon inhibition of the protein synthesis mTOR/4E-BP1 regulatory pathway which we found highly activated in primary cultures of α-SMA-positive CAFs, isolated from human PDAC resections.
  7. 07LabIn vitro (cells)Mechanism

    In human pancreatic cancer-associated fibroblasts, pasireotide inhibited synthesis of secreted proteins including IL-6.

    In plain wordsIn cells from human pancreatic cancers, pasireotide reduced production of secreted proteins including IL-6.

    Peptide
    Pasireotide
    Outcome
    DecreaseSecreted protein synthesis including IL-6
    Study

    humann: not reported in source

    Primary cancer-associated fibroblasts from pancreatic ductal adenocarcinoma
    Outcome group
    Receptor activity and mechanism · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The SOM230 analogue (Pasireotide) activates the sst1 receptor and inhibits the mTOR/4E-BP1 pathway and the resultant synthesis of secreted proteins including IL-6.
    1 context sentence
    Summary · context
    Our results demonstrate that CAF secretome-triggered chemoresistance is abolished upon inhibition of the protein synthesis mTOR/4E-BP1 regulatory pathway which we found highly activated in primary cultures of α-SMA-positive CAFs, isolated from human PDAC resections.

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

    28 Oct 2026, 02:03 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:34 UTC

    First added · source update from Europe PMC

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