| BackgroundThere have been a lot of basic researches and clinical studies confirmed that type2diabetes and tumor had many potential common risk factors, such as inflammatory,immunity, genetic, and environmental factors, after Professor Maynard proposed thatdiabetes may be associated with tumor in1910. For these reasons, patients with type2diabetes were more susceptible to tumor compared with non-diabetic patients. So, theeffects of antidiabetic druges on occurrence and development of tumor in type2diabetes ortype2diabetes patients with tumor became the hotspot for research. New antidiabetic drugs,such as GLP-1receptor agonists and DPP4inhibitors, are widely used in clinical, and moreand more researchers focused on their effects on occurrence and development of tumor intype2diabetes mellitus patients. Studies have to demonstrated that the GLP-1receptoragonists did not increase the risk of new-onset of tumor (such as pancreatic cancer, thyroidcancer,.etc) in type2diabetes. But studies about the effects of GLP-1receptor agonists intype2diabetes with tumor were lack. A study have mentioned that DPP4inhibitors did notaffect the risk of new-onset of tumor in type2diabetes, but the study had some limitations,and the results must be viewed with caution. First of all, DPP4inhibitor combination withother antidiabetic drugs were used in this study, and this might affect the accuracy of theresults. Secondly, the study did not analysis the effect of DPP4inhibitors on the risk ofnew-onset of a particular tumor.Objective1. To observe the impact of GLP-1receptor agonists on breast cancer cells, coloncancer cells and pancreatic cancer cells proliferation and migration in vitro, in order tofigure out the safety of the GLP-1receptor in type2diabetes patients with tumor.2. To assess the risk of DPP4inhibitor on new-onset of tumor, as well as particulartumor (such as skin cancer, hepatoma,.etc), in type2diabetes patients by meta analysis, in order to provide referance for the clinical decision-making.MethodsExperiment was divided into two parts, the first part was basic research, Breast cancercell line MDA-MB-231, colon cancer cell line HCT116and pancreatic cancer cell lineHS766T were selected as experimental subjects. Each cells were divided into control group,metformin group and exenatide group. Tumor cells proliferation were detected by CCK-8at72hours post exenatide intervention; tumor cells migration were observed by Transwellchamber method after12hours of culturing.The second part was clinical research. A comprehensive literature search in Embase,Pubmed and Cochrane database (up to April30,2013) was carried out to identify allclinical trails (randomized) published in English and Chinese that evaluated the efficacyand safety of DPP4inhibitor in type2diabetes treatment. At the same time, completed butunpublished clinical trails aslo searched in Clinicaltrials database. Review Manager(RevMan), version5.1(The Nordic Cochrane Centre, Copenhagen, Demark) software wasused for data analysis. Heterogeneity between studies was assessed by I2. Odds ratio wascalculated by random effects model to assess whether DPP4inhibitors could increase therisk of new-onset of tumor in type2diabetes patients.ResultsExenatide, a GLP-1receptor agonist, may inhibit proliferation of breast cancer cellline MDA-MB-231(P <0.01), colon cancer cell line HCT116(P <0.05), but have no effecton proliferation of pancreatic cancer cell line HS766T (p>0.05); it can also inhibitmigration of breast cancer cell line MDA-MB-231(18.10±5.82, P <0.01) and colon cancercell line HCT116(21.20±5.35, P <0.05), but can significantly increase the migration ofpancreatic cancer cell line HS766T (165.40±21.66, P <0.01).A total number of113patients suffering from tumor in both DPP4inhibitor treatmentgroup and control group(72in DPP4inhibitor group,41in the control group, heterogeneity:I2=16%, p=0.23) was reported in26clinical studies. Compared with control group, DPP4inhibitor did not increase the risk of cancer (OR=0.98,95%CI0.59-1.61).8studies havereported skin cancer(heterogeneity: I2=0%, p=0.53) and4studies have reportedhepatoma (heterogeneity: I2=0%, P=0.91) in subgroup analysis. Compared with controlgroup, DPP4inhibitor did not increase the risk of skin cancer (OR=1.00,95%CI0.39-2.54) and hepatoma (OR=0.85,95%CI0.17-4.22).ConclusionFrom the above results, we can speculate that GLP-1receptor agonist exenatide can beused for type2diabetes patients with breast cancer or colon cancer, but the usage ofexenatide in type2diabetes patients with pancreatic cancer is not recommended. DPP4inhibitor does not increase the risk of cancer in type2diabetes patients. However, this isonly a preliminary study, we also need further study on the mechanism of GLP-1receptoragonist exenatide affecting tumor cell proliferation and migration, on the impact of DPP4inhibitors on biological characteristics of tumor cells. In short, it is meaningful tosystemically evaluate the effects of antidiabetic drugs on occurrence and development oftumor, and this may influence the choice of antidiabetic drugs in type2diabetes mellituspatients with or without tumor. |
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