Retraction notice to "Potential of ß-elemene induced ferroptosis through Pole2-mediated p53 and PI3K/AKT signaling in lung cancer cells" [Chem. Biol. Interact. 365 (25 September 2022) 110088].

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Potential of ß-elemene induced ferroptosis through Pole2-mediated p53 and PI3K/AKT signaling in lung cancer cells.

Ferroptosis is crucial for tumor growth inhibition. Moreover, ferroptosis has been considered as a potential strategy against cancer. The present study focused on the mechanism of ferroptosis induction by ß-elemene during the lung cancer (extracted from the Chinese medicine Curcuma Wen yujin). CCK-8 assay, flow cytometry and biochemical assays including intracellular ROS, MDA, GSH, iron and 8-OHdG level were performed. DNA polymerase epsilon subunit 2 (Pole2) and the ferroptosis-related proteins were studied by utilizing western blotting. The study results showed that the ß-elemene reduced the viability of lung cancer cells via ferroptosis. Furthermore, multiple experiments confirmed that Pole2 knockdown enhanced the production of lipid ROS, MDA and iron, leading to the iron-dependent ferroptosis in lung cancer cells. Overexpression of Pole2 inhibited ß-elemene-induced ferroptosis through reduction of iron-dependent oxidative damage. Mechanically, Pole2 reduced the upregulation of p53 expression, and increased the phosphorylation levels of PI3K and AKT in ß-elemene-induced cells. Overexpression of TP53 or the inhibitor of PI3K/AKT pathway reversed the effects of Pole2. Together, ß-elemene evoked ferroptosis through the Pole2-regulated p53 or PI3K/AKT signalling, and might be an effective therapy for lung carcinogenesis.

Construction and Evaluation of Traceable rhES-QDs-M-MS Protein Delivery System: Sustained-Release Properties, Targeted Effect, and Antitumor Activity.

Recombinant human endostatin (rhES) is a protein drug with poor stability and short in vivo circulation time. The present study was therefore aimed at developing sustained-release lung targeted microspheres drug delivery system and evaluating its targeting efficiency using in vivo imaging techniques with quantum dots (QDs) as the imaging material. The oil-soluble QDs were coated with amphiphilic polymers to obtain a polymer-quantum dots micelle (QDs-M) with the potential to stably disperse in water. The rhES and QDs-M were combined using covalent bonds. The rhES-QDs-M microspheres (rhES-QDs-M-MS) were prepared using electrostatic spray technology and also evaluated via in vivo imaging techniques. The pharmacodynamics was further studied in mice. The rhES-QDs-M-MS (4-8 µm) were stable in an aqueous medium with good optical properties. The in vitro studies showed that the rhES-QDs-M-MS had sustained release which was maintained for at least 15 days (cumulative release >80%) without any burst release. The rhES-QDs-M-MS had a very high safety profile and also effectively inhibited the in vitro proliferation of human umbilical vein endothelial cells by about 70%. The pharmacokinetic results showed that the rhES could still be detected at 72 h in the experimental group which meant that the rhES-QDs-M-MS had a significant sustained-release effect. The rhES-QDs-M-MS had a better lung targeting effect and higher antitumor activity compared with the rhES. The traceable rhES-QDs-M-MS served as a promising drug delivery system for the poorly stable rhES proteins and significantly increased its lung-targeted effect, sustained-release properties, and antitumor activities.

A high bioavailability and sustained-release nano-delivery system for nintedanib based on electrospray technology.

BACKGROUND: Nintedanib is a new tyrosine kinase inhibitor and growth factor antagonist. It can be used to treat idiopathic pulmonary fibrosis diseases. Nintedanib has poor solubility in the intestinal tract environment, which leads to low bioavailability of just 4.7%. METHODS: In this study, a nintedanib solid dispersion was prepared by electrospray technology with an optimized formula (nintedanib:PVPK30:Soybean lecithin=1:5:0.25) and electrospray parameters (21 kV voltage, 18 cm receiving distance, 0.3 mL/h solution flow rate, 0.5 mm pinhole inner diameter). RESULTS: The accumulative release rate of the optimized solid dispersion was more than 60% in 30 minutes and 100% in 60 minutes. The size distribution was uniform and the surface observed with scanning electron microscopy (SEM) was smooth. The DSC and X-ray diffraction results showed that nintedanib existed in the solid dispersion through an amorphous form. Nintedanib solid dispersion sustained-release capsules were prepared to prolong drug release, improve patient compliance and reduce side effects. The accumulative release rate from the sustained release capsules was 35.17%, 54.78%, 70.58%, and 93.93% after 2 h, 6 h, 8 h, and 12 h, respectively, having obvious sustained release effects in vitro. The release behavior of solid dispersion sustained-release capsules in vitro was in accordance with the Ritger-Peppas model. The in vivo studies of nintedanib soft capsules, solid dispersion and nintedanib sustained release capsules in SD rats were investigated; the results showed that the Tmax of the soft capsule, solid dispersion and sustained release capsules were 3 h, 2 h, and 6 h, respectively. The Cmax were 2.945 mg/mL, 5.32 mg/mL, and 3.75 mg/mL, respectively, while the AUC0-24 h was 15.124 mg·h/mL, 23.438 mg·h/mL, and 24.584 mg·h/mL, respectively. The relevant bioavailability of the sustained-release capsules was 162.55% compared to the nintedanib soft capsule and 104.89% compared to the nintedanib solid dispersion. CONCLUSION: The results suggested superior bioavailability and a sustained-release effect from nintedanib sustained-release capsules, as compared to the reference (commercial nintedanib soft capsule).