Metformin-Sensitized Chemotherapy of Docetaxel Nanoemulsions Based on a Sequential Administration
<b>Background:</b> Chemotherapy has a broad-spectrum anti-tumor effect and is still the core strategy for cancer treatment. However, the side effects caused by its cytotoxicity, the chemoresistance caused by tumor heterogeneity and abnormal microenvironment seriously restrict the efficac...
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MDPI AG
2025-06-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/17/7/812 |
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| author | Junlei Zhang Jiapeng Mao Yilong Hu Xingze Huang Jian You Lihua Luo |
| author_facet | Junlei Zhang Jiapeng Mao Yilong Hu Xingze Huang Jian You Lihua Luo |
| author_sort | Junlei Zhang |
| collection | DOAJ |
| description | <b>Background:</b> Chemotherapy has a broad-spectrum anti-tumor effect and is still the core strategy for cancer treatment. However, the side effects caused by its cytotoxicity, the chemoresistance caused by tumor heterogeneity and abnormal microenvironment seriously restrict the efficacy of chemotherapy. Metformin presents the ability to sensitize chemotherapy by interfering with metabolic processes of tumor cells. However, as a dynamic process, metabolic intervention requires a specific time sequence law to optimize its role. <b>Methods:</b> Different administration sequences were screened by in vitro experiments to determine the optimal sequence of metformin and docetaxel. The anti-tumor effect of administration sequence in vivo was investigated in mouse models. The therapeutic advantages were comprehensively evaluated by tumor size, weight change, and survival rate. The immunofluorescent staining and transcriptome analysis were performed to study the mechanisms of the sequential administration strategy. <b>Results:</b> Compared with the subsequent administration and concurrent administration, pretreatment with metformin exhibited a stronger ability toward cell cycle arrest and tumor inhibition with low-dose docetaxel. Moreover, this pre-administration sequence could enhance the anti-tumor immune responses and prevent postoperative recurrence. <b>Conclusions:</b> The optimized chemotherapy sensitization mediated by metabolic intervention required an appropriate administration sequence, which also strengthened the anti-tumor immune responses. |
| format | Article |
| id | doaj-art-03b45293ce9c446784c3f20b60c75014 |
| institution | DOAJ |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-03b45293ce9c446784c3f20b60c750142025-08-20T02:47:10ZengMDPI AGPharmaceutics1999-49232025-06-0117781210.3390/pharmaceutics17070812Metformin-Sensitized Chemotherapy of Docetaxel Nanoemulsions Based on a Sequential AdministrationJunlei Zhang0Jiapeng Mao1Yilong Hu2Xingze Huang3Jian You4Lihua Luo5College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, ChinaCollege of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, ChinaCollege of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, ChinaInstitute of Biochemistry, College of Life Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, ChinaCollege of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, ChinaCollege of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China<b>Background:</b> Chemotherapy has a broad-spectrum anti-tumor effect and is still the core strategy for cancer treatment. However, the side effects caused by its cytotoxicity, the chemoresistance caused by tumor heterogeneity and abnormal microenvironment seriously restrict the efficacy of chemotherapy. Metformin presents the ability to sensitize chemotherapy by interfering with metabolic processes of tumor cells. However, as a dynamic process, metabolic intervention requires a specific time sequence law to optimize its role. <b>Methods:</b> Different administration sequences were screened by in vitro experiments to determine the optimal sequence of metformin and docetaxel. The anti-tumor effect of administration sequence in vivo was investigated in mouse models. The therapeutic advantages were comprehensively evaluated by tumor size, weight change, and survival rate. The immunofluorescent staining and transcriptome analysis were performed to study the mechanisms of the sequential administration strategy. <b>Results:</b> Compared with the subsequent administration and concurrent administration, pretreatment with metformin exhibited a stronger ability toward cell cycle arrest and tumor inhibition with low-dose docetaxel. Moreover, this pre-administration sequence could enhance the anti-tumor immune responses and prevent postoperative recurrence. <b>Conclusions:</b> The optimized chemotherapy sensitization mediated by metabolic intervention required an appropriate administration sequence, which also strengthened the anti-tumor immune responses.https://www.mdpi.com/1999-4923/17/7/812metformindocetaxelchemotherapyadministration sequence |
| spellingShingle | Junlei Zhang Jiapeng Mao Yilong Hu Xingze Huang Jian You Lihua Luo Metformin-Sensitized Chemotherapy of Docetaxel Nanoemulsions Based on a Sequential Administration Pharmaceutics metformin docetaxel chemotherapy administration sequence |
| title | Metformin-Sensitized Chemotherapy of Docetaxel Nanoemulsions Based on a Sequential Administration |
| title_full | Metformin-Sensitized Chemotherapy of Docetaxel Nanoemulsions Based on a Sequential Administration |
| title_fullStr | Metformin-Sensitized Chemotherapy of Docetaxel Nanoemulsions Based on a Sequential Administration |
| title_full_unstemmed | Metformin-Sensitized Chemotherapy of Docetaxel Nanoemulsions Based on a Sequential Administration |
| title_short | Metformin-Sensitized Chemotherapy of Docetaxel Nanoemulsions Based on a Sequential Administration |
| title_sort | metformin sensitized chemotherapy of docetaxel nanoemulsions based on a sequential administration |
| topic | metformin docetaxel chemotherapy administration sequence |
| url | https://www.mdpi.com/1999-4923/17/7/812 |
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