دورية أكاديمية
Efficacy of Metformin and Chemotherapeutic Agents on the Inhibition of Colony Formation and Shh/Gli1 Pathway: Metformin/Docetaxel Versus Metformin/5-Fluorouracil.
| العنوان: | Efficacy of Metformin and Chemotherapeutic Agents on the Inhibition of Colony Formation and Shh/Gli1 Pathway: Metformin/Docetaxel Versus Metformin/5-Fluorouracil. |
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| المؤلفون: | Fatehi-Agdam M; Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil.; Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil., Vatankhah MA; Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil.; Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil., Panahizadeh R; Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil.; Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil., Jeddi F; Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil., Najafzadeh N; Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil. |
| المصدر: | Drug research [Drug Res (Stuttg)] 2021 Jan; Vol. 71 (1), pp. 17-25. Date of Electronic Publication: 2020 Sep 28. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Thieme Country of Publication: Germany NLM ID: 101602406 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2194-9387 (Electronic) Linking ISSN: 21949379 NLM ISO Abbreviation: Drug Res (Stuttg) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Stuttgart : Thieme |
| مواضيع طبية MeSH: | Tumor Stem Cell Assay*, Antineoplastic Combined Chemotherapy Protocols/*pharmacology , Metformin/*pharmacology , Stomach Neoplasms/*drug therapy, Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cell Line, Tumor ; Docetaxel/pharmacology ; Docetaxel/therapeutic use ; Drug Synergism ; Fluorouracil/pharmacology ; Fluorouracil/therapeutic use ; Gene Expression Regulation, Neoplastic/drug effects ; Hedgehog Proteins/metabolism ; Humans ; Metformin/therapeutic use ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Stomach Neoplasms/pathology ; Zinc Finger Protein GLI1/metabolism |
| مستخلص: | Background: Gastric cancer is a common gastrointestinal cancer characterized by poor prognosis and chemoresistance. Docetaxel and 5-fluorouracil (5-FU) are frequently used for the treatment of gastric cancer. Despite their potent anti-cancer effects, chemoresistance occurs in metastatic gastric cancer. Metformin, a popular anti-diabetic drug, has been proven to have potent anticancer effects on gastrointestinal cancers. Here, we aim to improve this chemotherapy agents' efficacy by pretreatment with metformin. Methods: The AGS gastric cancer cell line were pretreated with three different sub-toxic concentration of metformin and then treated with various concentrations of 5-FU and docetaxel.The anticancer effects of the combination of metformin with the chemotherapy agents were determined using clonogenic assay and DAPi staining. We used real-time PCR to evaluate Gli1 , Gli2 , and TWIST1 mRNA expression levels in the gastric cancer cells. Also, the expression of the Shh protein was assessed using immunocytochemistry. Results: Here, we found that metformin sensitized the gastric cancer cells to chemotherapy. The combination treatments were more effective in reducing the number of cancer colonies compared to 5-FU or docetaxel alone. The combination of metformin with 5-FU or docetaxel significantly reduced the number of cells expressing the Shh protein compared to the 5-FU alone or docetaxel alone. Interestingly, we found that the combination of metformin with docetaxel significantly down-regulated the mRNA levels of Gli1 , Gli2 , and TWIST1 in the AGS gastric cancer cell line compared to docetaxel alone. Conclusion: Overall, our data strongly support an important role for metformin as an enhancer of the efficacy of chemotherapeutic agents against gastric cancer. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All authors declare that they have no conflict of interest. (Thieme. All rights reserved.) |
| معلومات مُعتمدة: | M.Sc. and a medical student research IR.ARUMS.REC.1397.240; Ardabil University of Medical Sciences IR.ARUMS.REC.1398.418 |
| المشرفين على المادة: | 0 (GLI1 protein, human) 0 (Hedgehog Proteins) 0 (SHH protein, human) 0 (Zinc Finger Protein GLI1) 15H5577CQD (Docetaxel) 9100L32L2N (Metformin) U3P01618RT (Fluorouracil) |
| تواريخ الأحداث: | Date Created: 20200928 Date Completed: 20210913 Latest Revision: 20210913 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1055/a-1248-9008 |
| PMID: | 32987433 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2194-9387 |
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| DOI: | 10.1055/a-1248-9008 |