Delivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer
| Autor: | Peng-Ke Yan, Wen-Ting Zhu, Yi-Qing Chen, Zhong-Wen Yuan, Cai-Yan Lin, Zhen-Hua Li |
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| Rok vydání: | 2020 |
| Předmět: |
Biodistribution
Biophysics Pharmaceutical Science rapamycin liposomes Bioengineering Antineoplastic Agents Apoptosis colorectal cancer 02 engineering and technology 010402 general chemistry 01 natural sciences Biomaterials Inhibitory Concentration 50 Mice In vivo International Journal of Nanomedicine Cell Movement Cell Line Tumor Drug Discovery Distribution (pharmacology) Animals Humans MTT assay Tissue Distribution 5-fluorouracil Particle Size PI3K/AKT/mTOR pathway Tumor Stem Cell Assay Cell Proliferation Original Research Sirolimus Liposome P53 Chemistry Organic Chemistry Drug Synergism General Medicine Akt/mTOR 021001 nanoscience & nanotechnology Xenograft Model Antitumor Assays In vitro 0104 chemical sciences Liposomes Cancer research Fluorouracil 0210 nano-technology Colorectal Neoplasms Signal Transduction |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 |
| Popis: | Yi-Qing Chen,* Wen-Ting Zhu,* Cai-Yan Lin, Zhong-Wen Yuan, Zhen-Hua Li, Peng-Ke Yan The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng-Ke YanThe Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, People’s Republic of ChinaEmail gysyypk@126.comBackground: Rapamycin is a promising agent for treating tumors, but clinical applications of rapamycin are limited due to its poor water solubility and low bioavailability. This paper constructs a liposome delivery system for rapamycin to improve the effect in treating colorectal cancer.Methods: We prepared the rapamycin liposomes using the ethanol injection method. The cellular uptake and biodistribution were detected by LC-MS and in vivo imaging system. MTT assay, transwell migration experiment, flow cytometry, and Western blot analysis evaluated the antitumor effect of rapamycin liposomes in vitro. Furthermore, HCT-116 tumor-bearing mice were used to assess the therapeutic efficacy of rapamycin liposomes in vivo.Results: The prepared rapamycin liposomes had a particle size of 100± 5.5 nm and with a narrow size distribution. In vitro cellular uptake experiments showed that the uptake of rapamycin liposomes by colorectal cells was higher than that of free rapamycin. Subsequently, in vivo imaging experiments also demonstrated that rapamycin liposomes exhibited higher tumor accumulation. Therefore, the ability of rapamycin liposomes to inhibit tumor proliferation, migration and to induce tumor apoptosis is superior to that of free rapamycin. We also demonstrated in vivo good antitumor efficacy of the rapamycin liposomes in HCT-116 xenograft mice. In addition, rapamycin liposomes and 5-FU can synergistically improve the efficacy of colorectal cancer via the Akt/mTOR and P53 pathways.Conclusion: Collectively, rapamycin liposomes are a potential treatment for colorectal cancer, as it not only improves rapamycin’s antitumor effect but also synergistically enhances 5-FU’s chemotherapy effect.Keywords: rapamycin liposomes, 5-fluorouracil, Akt/mTOR, P53, colorectal cancer |
| Databáze: | OpenAIRE |
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