Objective: Our study aimed to find potential biomarkers for drug resistance in liver cancer cells using metabolomics and further to evaluate the potential of psoralen-loaded polymer lipid nanoparticles (PSO-PLNs) to reverse the resistance of cells to doxorubicin. Methods: We used LC-MS-based non-targeted metabolomics, also known as global metabolite profiling, to screen in serum and urine of mice engrafted with a liver cancer cell line sensitive (HepG2/S) or resistant to doxorubicin (HepG2/ADR) for differentially regulated metabolites. We subsequently quantified the abundance of these metabolites in serum and the urine of mice. The mice were engrafted with HepG2 cells resistant against doxorubicin and were treated with I) doxorubicin, II) a combination of doxorubicin and psoralen and III) a combination of doxorubicin and psoralen packed in polymer lipid nanoparticles. Results: Metabolites found to be differentially present in urine of mice engrafted with resistant HepG2 cells were: hip...puric acid, hyaluronic acid, pantothenic acid, and betaine; retinoic acid and α-linolenic acid were found to be reduced in serum samples of mice with HepG2 cells resistant to doxorubicin. The targeted analysis showed that the degree of regression of metabolic markers in groups differed: treatment group 2 had stronger degree of regression than treatment group 1 and the negative control group had the smallest, which indicates that the PSO-PLNs have superior properties compared with other treatments. Conclusion: Psoralen reverses drug resistance of liver cancer cells and its efficacy can be increased by encapsulation in polymer lipid nanoparticles.
TY - JOUR
AU - Li, Lihong
AU - Zou, Tengteng
AU - Liang, Min
AU - Mezhuev, Yaroslav
AU - Tsatsakis, Aristidis Michael
AU - Buha-Đorđević, Aleksandra
AU - Lan, Meng
AU - Liu, Fengjie
AU - Cai, Tiange
AU - Gong, Peng
AU - Cai, Yu
PY - 2021
UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3911
AB - Objective: Our study aimed to find potential biomarkers for drug resistance in liver cancer cells using metabolomics and further to evaluate the potential of psoralen-loaded polymer lipid nanoparticles (PSO-PLNs) to reverse the resistance of cells to doxorubicin. Methods: We used LC-MS-based non-targeted metabolomics, also known as global metabolite profiling, to screen in serum and urine of mice engrafted with a liver cancer cell line sensitive (HepG2/S) or resistant to doxorubicin (HepG2/ADR) for differentially regulated metabolites. We subsequently quantified the abundance of these metabolites in serum and the urine of mice. The mice were engrafted with HepG2 cells resistant against doxorubicin and were treated with I) doxorubicin, II) a combination of doxorubicin and psoralen and III) a combination of doxorubicin and psoralen packed in polymer lipid nanoparticles. Results: Metabolites found to be differentially present in urine of mice engrafted with resistant HepG2 cells were: hippuric acid, hyaluronic acid, pantothenic acid, and betaine; retinoic acid and α-linolenic acid were found to be reduced in serum samples of mice with HepG2 cells resistant to doxorubicin. The targeted analysis showed that the degree of regression of metabolic markers in groups differed: treatment group 2 had stronger degree of regression than treatment group 1 and the negative control group had the smallest, which indicates that the PSO-PLNs have superior properties compared with other treatments. Conclusion: Psoralen reverses drug resistance of liver cancer cells and its efficacy can be increased by encapsulation in polymer lipid nanoparticles.
PB - Elsevier B.V.
T2 - European Journal of Pharmaceutics and Biopharmaceutics
T1 - Screening of metabolites in the treatment of liver cancer xenografts HepG2/ADR by psoralen-loaded lipid nanoparticles
VL - 165
SP - 337
EP - 344
DO - 10.1016/j.ejpb.2021.05.025
ER -
@article{
author = "Li, Lihong and Zou, Tengteng and Liang, Min and Mezhuev, Yaroslav and Tsatsakis, Aristidis Michael and Buha-Đorđević, Aleksandra and Lan, Meng and Liu, Fengjie and Cai, Tiange and Gong, Peng and Cai, Yu",
year = "2021",
abstract = "Objective: Our study aimed to find potential biomarkers for drug resistance in liver cancer cells using metabolomics and further to evaluate the potential of psoralen-loaded polymer lipid nanoparticles (PSO-PLNs) to reverse the resistance of cells to doxorubicin. Methods: We used LC-MS-based non-targeted metabolomics, also known as global metabolite profiling, to screen in serum and urine of mice engrafted with a liver cancer cell line sensitive (HepG2/S) or resistant to doxorubicin (HepG2/ADR) for differentially regulated metabolites. We subsequently quantified the abundance of these metabolites in serum and the urine of mice. The mice were engrafted with HepG2 cells resistant against doxorubicin and were treated with I) doxorubicin, II) a combination of doxorubicin and psoralen and III) a combination of doxorubicin and psoralen packed in polymer lipid nanoparticles. Results: Metabolites found to be differentially present in urine of mice engrafted with resistant HepG2 cells were: hippuric acid, hyaluronic acid, pantothenic acid, and betaine; retinoic acid and α-linolenic acid were found to be reduced in serum samples of mice with HepG2 cells resistant to doxorubicin. The targeted analysis showed that the degree of regression of metabolic markers in groups differed: treatment group 2 had stronger degree of regression than treatment group 1 and the negative control group had the smallest, which indicates that the PSO-PLNs have superior properties compared with other treatments. Conclusion: Psoralen reverses drug resistance of liver cancer cells and its efficacy can be increased by encapsulation in polymer lipid nanoparticles.",
publisher = "Elsevier B.V.",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
title = "Screening of metabolites in the treatment of liver cancer xenografts HepG2/ADR by psoralen-loaded lipid nanoparticles",
volume = "165",
pages = "337-344",
doi = "10.1016/j.ejpb.2021.05.025"
}
Li, L., Zou, T., Liang, M., Mezhuev, Y., Tsatsakis, A. M., Buha-Đorđević, A., Lan, M., Liu, F., Cai, T., Gong, P.,& Cai, Y.. (2021). Screening of metabolites in the treatment of liver cancer xenografts HepG2/ADR by psoralen-loaded lipid nanoparticles. in European Journal of Pharmaceutics and Biopharmaceutics
Elsevier B.V.., 165, 337-344.
https://doi.org/10.1016/j.ejpb.2021.05.025
Li L, Zou T, Liang M, Mezhuev Y, Tsatsakis AM, Buha-Đorđević A, Lan M, Liu F, Cai T, Gong P, Cai Y. Screening of metabolites in the treatment of liver cancer xenografts HepG2/ADR by psoralen-loaded lipid nanoparticles. in European Journal of Pharmaceutics and Biopharmaceutics. 2021;165:337-344.
doi:10.1016/j.ejpb.2021.05.025 .
Li, Lihong, Zou, Tengteng, Liang, Min, Mezhuev, Yaroslav, Tsatsakis, Aristidis Michael, Buha-Đorđević, Aleksandra, Lan, Meng, Liu, Fengjie, Cai, Tiange, Gong, Peng, Cai, Yu, "Screening of metabolites in the treatment of liver cancer xenografts HepG2/ADR by psoralen-loaded lipid nanoparticles" in European Journal of Pharmaceutics and Biopharmaceutics, 165 (2021):337-344,
https://doi.org/10.1016/j.ejpb.2021.05.025 . .
