Abstract
Cancer initiation and protection mainly derives from a systemic metabolic environment regulated by dietary patterns. Less is known about the impact of nutritional interventions in people with a diagnosis of cancer. The aim of our study was to investigate the effect of a diet rich in resistant starch (RS) on cell pathways modulation and metabolomic phenotype in pancreatic cancer xenograft mice. RNA-Seq experiments on tumor tissue showed that 25 genes resulted in dysregulated pancreatic cancer in mice fed with an RS diet, as compared to those fed with control diet. Moreover, in these two different mice groups, six serum metabolites were deregulated as detected by LC–MS analysis. A bioinformatic prediction analysis showed the involvement of the differentially expressed genes on insulin receptor signaling, circadian rhythm signaling, and cancer drug resistance among the three top canonical pathways, whilst cell death and survival, gene expression, and neurological disease were among the three top disease and biological functions. These findings shed light on the genomic and metabolic phenotype, contributing to the knowledge of the mechanisms through which RS may act as a potential supportive approach for enhancing the efficacy of existing cancer treatments.
Highlights
Epidemiologic studies revealed associations between aspects of diet, nutrition, and physical activity with cancers, which are the second most important cause of death globally, after cardiovascular disease, considering all of the non-communicable diseases
We investigate the effect of this diet with a high content of resistant starch (RS) on the gene expression and metabolomics profile, and its implication on cell pathways modulation in pancreatic cancer xenograft mice
We analyzed the gene expression profiles in PC xenograft mice fed with the control diet and the RS diet
Summary
Epidemiologic studies revealed associations between aspects of diet, nutrition, and physical activity with cancers, which are the second most important cause of death globally, after cardiovascular disease, considering all of the non-communicable diseases (http://www.who.int/en/news-room/fact-sheets/detail/cancer). Pancreatic cancer incidence is expected to rise in the near future It is currently the third leading cause of cancer death worldwide [2], and it is expected to become the second by 2030 [3]. With a five-year survival rate of less than 5% for patients with a resectable disease [4], and an average survival time of six months for patients with advanced metastasized disease [5], pancreatic cancer is one of the most aggressive and fatal malignancies, with a tremendously poor prognosis. The reason for this extremely short survival time may be due to the very slow evolution of the disease, lasting up to 18 years from the time of the initiating mutations in pre-cancerous lesions to the metastatic disease [6]
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