Antidiabetic drugs influence molecular mechanisms in prostate cancer
| Autor: | Georg Schäfer, Andrea Eigentler, Martin Zieher, Eberhard Steiner, Isabel Heidegger, Helmut Klocker, Josef Fritz, Andreas Pircher, Martin Puhr, Renate Pichler, Wolfgang Horninger |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Oncology insulin Cancer Research medicine.medical_specialty Biopsy medicine.medical_treatment Kaplan-Meier Estimate urologic and male genital diseases 03 medical and health sciences Prostate cancer 0302 clinical medicine Recurrence Internal medicine Diabetes mellitus Humans Hypoglycemic Agents Medicine Aged Neoplasm Staging Pharmacology business.industry Insulin Prostatic Neoplasms Middle Aged aggressiveness Prognosis medicine.disease mortality Metformin 030104 developmental biology Diabetes Mellitus Type 2 Receptors Androgen 030220 oncology & carcinogenesis Molecular Medicine Neoplasm Grading metformin business molecular pathways Biomarkers Research Paper medicine.drug |
| Zdroj: | Cancer Biology & Therapy |
| ISSN: | 1555-8576 1538-4047 |
| Popis: | Background: We investigated the role of diabetes mellitus (DM) and the molecular mechanisms of antidiabetic drugs in prostate cancer (PCa). Patients and Methods: 167 patients with both DM and PCa underwent radical prostatectomy (RPE). We divided our patient collective into “metformin” users, “insulin” users, “other antidiabetic drug” users and those with “no antidiabetic drug/diet only” (control group) and analyzed differences in PCa aggressiveness and laboratory parameters among treatment groups. In addition, we generated a tissue-micro-array (TMA) from RPE specimens for the analysis of candidate target pathways of antidiabetic drugs by immunohistochemistry (IHC). Results: Gleason score of both biopsy and RPE, biopsy undergrading, tumor stage as well as positive resection margins did not significantly change among groups. Preoperative body mass-index, PSA, fPSA and prostate volume/weight did not change among the treatment groups. As well, CRP, GOT, GPT, yGT, LDH, amylase, hemoglobin, TSH, FT3 and FT4 did not differ. Metformin or insulin use was not associated with changes in biochemical tumor recurrence or PCa specific mortality rates. However, tissue TMA analyses by IHC showed decreased mTOR activation, as indicated by phospho-mTOR in cancer tissue of patients with metformin and also with insulin use compared to the control group. In addition, we were able to show that the androgen receptor and the epithelial-cell contact marker E-cadherin decreased upon metformin use compared to the control group. Conclusion: We did not find a connection between antidiabetic drugs and PCa aggressiveness or progression. However, tumor biology seems to be different among patients with and without antidiabetic drugs. |
| Databáze: | OpenAIRE |
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