Repeated trans-arterial treatments of LDL-DHA nanoparticles induce multiple pathways of tumor cell death in hepatocellular carcinoma bearing rats.

Autor:	Wang Y; Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan, China.; Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, United States., Li J; Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, United States., do Vale GD; Center for Human Nutrition and Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, United States., Chaudhary J; Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, United States., Anwar A; Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, United States., McDonald JG; Center for Human Nutrition and Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, United States., Qin T; Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan, China., Zhang H; Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan, China., Corbin IR; Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, United States.; Internal Medicine Division of Liver and Digestive Diseases, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, United States.; Radiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2022 Nov 24; Vol. 12, pp. 1052221. Date of Electronic Publication: 2022 Nov 24 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.1052221
Abstrakt:	Introduction: Repeated hepatic arterial delivery of therapeutic agents to the liver by percutaneously implanted port-catheter systems has been widely used to treat unresectable liver cancer. This approach is applied to assess the therapeutic efficacy of repeated low-density lipoprotein-docosahexaenoic acid (LDL-DHA) nanoparticle treatments in a rat model of hepatocellular carcinoma. Methods: N1S1 hepatoma bearing rats underwent placement of a percutaneously implanted hepatic artery port-catheter system and were allocated to untreated, control LDL-triolein (LDL-TO) or LDL-DHA nanoparticle infusions groups. Treatments were performed every three days over a nine day study period. MRI was performed at baseline and throughout the study. At the end of the study tissue samples were collected for analyses. Results and Discussion: Implantation of the port catheters was successful in all rats. MRI showed that repeated infusions of LDL-DHA nanoparticles significantly impaired the growth of the rat hepatomas eventually leading to tumor regression. The tumors in the LDL-TO treated group showed delayed growth, while the untreated tumors grew steadily throughout the study. Histopathology and MRI support these findings demonstrating extensive tumor necrosis in LDL-DHA treated groups while the control groups displayed minor necrosis. Molecular and biochemical analyses also revealed that LDL-DHA treated tumors had increased levels of nuclear factor-kappa B and lipid peroxidation and depletion of glutathione peroxidase 4 relative to the control groups. Evidence of both ferroptosis and apoptosis tumor cell death was observed following LDL-DHA treatments. In conclusion repeated transarterial infusions of LDL-DHA nanoparticles provides sustained repression of tumor growth in a rat hepatoma model. 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. (Copyright © 2022 Wang, Li, Vale, Chaudhary, Anwar, McDonald, Qin, Zhang and Corbin.)
Databáze:	MEDLINE
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