Combination of metformin with chemotherapeutic drugs via different molecular mechanisms
| Autor: | Caimei He, Xiaoping Yang, Mei Peng, Zhao-Qian Liu, Kwame Oteng Darko, Ting Tao, Yanjun Huang, Tao Yin, Qiongli Su |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Drug Antimetabolites Antineoplastic Paclitaxel media_common.quotation_subject Deoxycytidine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Estrogen Receptor Modulators Neoplasms Antineoplastic Combined Chemotherapy Protocols Humans Medicine Radiology Nuclear Medicine and imaging Cyclophosphamide PI3K/AKT/mTOR pathway media_common Insulin-like growth factor 1 receptor Antibiotics Antineoplastic business.industry Mechanism (biology) AMPK Androgen Antagonists General Medicine Gemcitabine Metformin Tubulin Modulators Methotrexate 030104 developmental biology Oncology chemistry 030220 oncology & carcinogenesis Cancer research Fluorouracil Cisplatin Signal transduction business medicine.drug |
| Zdroj: | Cancer Treatment Reviews. 54:24-33 |
| ISSN: | 0305-7372 |
| DOI: | 10.1016/j.ctrv.2017.01.005 |
| Popis: | Metformin, a widely prescribed drug for treating type II diabetes, is one of the most extensively recognized metabolic modulators which has shown an important anti-cancer property. However, fairly amount of clinical trials on its single administration have not demonstrated a convincing efficiency yet. Thus, recent studies tend to combine metformin with clinical commonly used chemotherapeutic drugs to decrease their toxicity and attenuate their tumor resistance. These strategies have displayed promising clinical benefits. Interestingly, metformin experiences a diversity of molecular mechanisms when it combines different chemotherapeutic drugs. For example, AMPK/mTOR signaling pathway activation plays a major role when it combines with hormone modulating drugs. In contrast, suppression of HIF-1, p-gp and MRP1 protein expression is its main mechanism when metformin combines with anti-metabolites. Furthermore, when combining of metformin with antibiotics, inhibition of oxidative stress and inflammatory signaling pathway becomes a novel pharmaceutical mechanism for its cardio-protective effect. Induction of apoptotic mitochondria and nucleus could be the major player for the synergistic effect of its combination with cisplatin. In contrast, down-regulation of lipoprotein or cholesterol synthesis might be the undefined molecular base when metformin combines with taxane. Thus, deep exploration of molecular mechanisms of metformin with these different drugs is critical to understand its synergistic effect and help for personalized administration. In this mini-review, detailed molecular mechanisms of these combinations are discussed and summarized. This work will promote better understanding of molecular mechanisms of metformin and provide precise targets to identify specific patient groups to achieve satisfactory treatment efficacy. |
| Databáze: | OpenAIRE |
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