Early treatment with metformin induces resistance against tumor growth in adult rats

Trombini, Amanda Bianchi; Franco, Claudinéia C. S.; Miranda, Rosiane Aparecida; Oliveira, Júlio Cézar de; Barella, Luiz F.; Prates, Kelly Valério; Souza, Aline Amenencia de; Pavanello, Audrei; Malta, Ananda; Almeida, Douglas Lopes; Tófolo, Laize Peron; Rigo, Kesia Palma; Ribeiro, Tatiane As; Fabricio, Gabriel Sérgio; Sant’Anna, Juliane Rocha de; Castro-Prado, Marialba Aa; Souza, Helenir Medri de; Morais, Hely de; Mathias, Paulo Cézar de Freitas

doi:10.4161/15384047.2014.962968

Cited by 5 publications

(8 citation statements)

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“…Animals that are of different ages when they receive the same stimulus might not respond with the same magnitude because they have differences regarding how they function (Trombini et al . ). The effect of the age of the host on the incidence and growth rate of the Walker 256 carcinosarcoma was investigated by Kerkvliet and Kimeldorf ().…”

Section: Discussionmentioning

confidence: 97%

“…) and vascularization during tumourigenesis (Trombini et al . ). Notwithstanding these restrictions, we found similar results in cellular proliferation from Walker 256 tumour‐bearing rats that underwent anaerobic exercise (Lima et al .…”

Section: Discussionmentioning

confidence: 97%

“…The rats were considered cachectic when their BWL was higher than 10% (Trombini et al . ). Metastases from the retroperitoneal region were also removed.…”

Section: Methodsmentioning

confidence: 97%

“…Using the same experimental carcinoma model associated with metformin treatment, starting early during adolescence, as well as later in the beginning of adulthood, different responses were obtained; the first treatment gives some resistance to the growth tumour, whereas the later one does not confer any resistance (Trombini et al . ). Recently, our group showed that aerobic exercise training applied during adolescence can be considered as a prevention cornerstone as a result of decreased tumour growth, metastatic foci and cancer‐related cachexia in adult rats (Moreira et al .…”

Section: Introductionmentioning

confidence: 97%

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Moderate exercise training since adolescence reduces Walker 256 tumour growth in adult rats

Moreira

Almeida

Franco

et al. 2019

The Journal of Physiology

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Key pointsr Cancer growth, cell proliferation and cachexia index can be attenuated by the beneficial programming effect of moderate exercise training, especially if it begins in adolescence.r Walker 256 tumour-bearing rats who started exercise training during adolescence did not revert the basal low glycaemia and insulinaemia observed before tumour cell inoculation.r The moderate exercise training improved glucose tolerance and peripheral insulin sensitivity only in rats exercised early in adolescence.r The chronic effects of our exercise protocol are be beneficial to prevent cancer cachexia and hold clear potential as a nonpharmacological therapy of insulin sensitization.Veridiana Mota Moreira has worked in higher education as an effective member of a research ethics committee, a co-ordinator of physical activity and health research laboratories, an editor and reviewer in major scientific journals, a professor in Physical Education, and in Nursing, Biology and Physiotherapy Degree Courses. She has supervised and co-ordinated monographs and internships in Physical Education. She has participated in a high-performance soccer team as a physiologist. She participates in the Developmental Origins of Health and Disease (DOHaD) research group at the Laboratory of Cellular Biology of Secretion co-ordinated by Paulo Cezar de Freitas Mathias. In the future, she intends to study the application of molecular biology techniques associated with cancer, aiming to understand the multiplicity of cellular networks involved in the response to physical training, providing mechanisms by which the muscular system communicates with other organs, and mediating the beneficial effects of physical exercise related to health at different ages. * These authors contributed equally to this work. AbstractWe tested the hypothesis that moderate exercise training, performed early, starting during adolescence or later in life during adulthood, can inhibit tumour cell growth as a result of changes in biometric and metabolic markers. Male rats that were 30 and 70 days old performed a treadmill running protocol over 8 weeks for 3 days week -1 , 44 min day -1 and at 55-65%V O 2 max . After the end of training, a batch of rats was inoculated with Walker 256 carcinoma cells. At 15 days after carcinoma cell inoculation, the tumour was weighed and certain metabolic parameters were evaluated. The data demonstrated that physical performance was better in rats that started exercise training during adolescence according to the final workload andV O 2 max . Early or later moderate exercise training decreased the cachexia index, cell proliferation and tumour growth; however, the effects were more pronounced in rats that exercised during adolescence. Low glycaemia, insulinaemia and tissue insulin sensitivity was not reverted in Walker 256 tumour-bearing rats who trained during adolescence. Cancer growth can be attenuated by the beneficial programming effect of moderate exercise training, especially if it begins during adolescence. In addition, improvement in glu...

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

“…The rats were considered cachectic when their BWL was higher than 10% (Trombini et al . ). Metastases from the retroperitoneal region were also removed.…”

Section: Methodsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

Moderate exercise training since adolescence reduces Walker 256 tumour growth in adult rats

Moreira

Almeida

Franco

et al. 2019

The Journal of Physiology

Self Cite

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“…Our laboratory previously demonstrated that metformin could suppress PC proliferation and also inhibit the survival of highly resistant fractions of CSCs/CSLCs screened from PC cells [ 38 ]. Based on preliminary work from our laboratory and others [ 39 , 40 ], metformin has been entered into multiple clinical trials (e.g. NCT01579812).…”

Section: Drug Repurposing Principles Of Network Pharmacology For Gi Cmentioning

confidence: 99%

Novel Holistic Approaches for Overcoming Therapy Resistance in Pancreatic and Colon Cancers

Sarkar

2015

Med Princ Pract

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Gastrointestinal (GI) cancers, such as of the colon and pancreas, are highly resistant to both standard and targeted therapeutics. Therapy-resistant and heterogeneous GI cancers harbor highly complex signaling networks (the resistome) that resist apoptotic programming. Commonly used gemcitabine or platinum-based regimens fail to induce meaningful (i.e. disease-reversing) perturbations in the resistome, resulting in high rates of treatment failure. The GI cancer resistance networks are, in part, due to interactions between parallel signaling and aberrantly expressed microRNAs (miRNAs) that collectively promote the development and survival of drug-resistant cancer stem cells with epithelial-to-mesenchymal transition (EMT) characteristics. The lack of understanding of the resistance networks associated with this subpopulation of cells as well as reductionist, single protein-/pathway-targeted approaches have made ‘effective drug design' a difficult task. We propose that the successful design of novel therapeutic regimens to target drug-resistant GI tumors is only possible if network-based drug avenues and agents, in particular ‘natural agents' with no known toxicity, are correctly identified. Natural agents (dietary agents or their synthetic derivatives) can individually alter miRNA profiles, suppress EMT pathways and eliminate cancer stem-like cells that derive from pancreatic cancer and colon cancer, by partially targeting multiple yet meaningful networks within the GI cancer resistome. However, the efficacy of these agents as combinations (e.g. consumed in the diet) against this resistome has never been studied. This short review article provides an overview of the different challenges involved in the understanding of the GI resistome, and how novel computational biology can help in the design of effective therapies to overcome resistance.

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Epigenetic programming for obesity and noncommunicable disease: From womb to tomb

Saavedra,

Piovan,

Moreira

et al. 2023

Rev Endocr Metab Disord

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Early treatment with metformin induces resistance against tumor growth in adult rats

Cited by 5 publications

References 50 publications

Moderate exercise training since adolescence reduces Walker 256 tumour growth in adult rats

Moderate exercise training since adolescence reduces Walker 256 tumour growth in adult rats

Novel Holistic Approaches for Overcoming Therapy Resistance in Pancreatic and Colon Cancers

Epigenetic programming for obesity and noncommunicable disease: From womb to tomb

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