Long non­coding RNA fer­1­like family member 4 serves as a tumor suppressor in laryngeal squamous cell carcinoma cells via regulating the AKT/ERK signaling pathway.

Laryngeal squamous cell carcinoma (LSCC) is a common type of malignant tumor of the head and neck. An increasing number of studies have illustrated that long non­coding RNAs (lncRNAs) serve an important role in the occurrence and development of LSCC. Therefore, the present study aimed to investigate the expression changes and mechanism of lncRNA fer­1­like family member 4 (FER1L4) in the progression of LSCC. The expression levels of FER1L4 in LSCC cell lines (AMC­HN­8, Tu 686, M4E and M2E) and a normal cell line (HBE135­E6E7) were analyzed using reverse transcription­quantitative PCR. The FER1L4 overexpression plasmid (plasmid­FER1L4) was subsequently transfected into Tu 686 cells to upregulate the expression levels of FER1L4. Cell viability was detected using a Cell Counting Kit­8 assay, cell proliferation was analyzed using a colony formation assay, apoptosis was examined by flow cytometry, and cell migration and invasion were determined using wound healing and Transwell assays, respectively. In addition, the plasmid­FER1L4 cells were also treated with insulin­like growth factor 1 (IGF­1) to determine the effect of FER1L4 on the AKT/ERK signaling pathway, and the effect of the plasmid­FER1L4 on the expression levels of AKT/ERK signaling pathway­related proteins were analyzed using western blotting. The results of the present study revealed that FER1L4 expression levels were downregulated in AMC­HN­8 and Tu 686 cells. Notably, FER1L overexpression significantly reduced the cell viability, proliferation, migration and invasion of LSCC cells, while promoting apoptosis. Meanwhile, the plasmid­FER1L4 also significantly suppressed the phosphorylation levels of AKT and ERK. Further studies indicated that the aforementioned changes could be reversed by IGF­1, indicating FER1L4 may regulate the progression of LSCC cells by inhibiting the AKT/ERK signaling pathway. In conclusion, the present study provided a potential novel direction for the treatment of LSCC in the future and suggested that FER1L4 may be a new target in this field.

Synergistically enhanced anticancer effect of codelivered curcumin and siPlk1 by stimuli-responsive α-lactalbumin nanospheres.

AIM: To achieve enhanced anticancer efficacy by combined siPlk1 and curcumin (cur) therapy using α-lactalbumin (α-lac) nanocarrier delivery. MATERIALS & METHODS: α-Lac was partially hydrolyzed into amphiphilic peptides, and then self-assembled into nanospheres (NS). Cur was loaded into their hydrophobic core during the self-assembly process. siPlk1-SH was cross-linked with the endogenous cysteines on the NS. CRGDK peptide was conjugated on NS to target integrins overexpressed in HeLa cells. RESULTS & CONCLUSION: The Cur and siPlk1 coloaded NS formulations possessed an enhanced tumor targeting and antitumor properties. Drugs were responsively released from disulfide bonds cross-linked RGD-NS/Cur/siPlk1 corresponding to the high intracellular glutathione concentrations of cancer cells. Both in vitro cell viability experiments and in vivo antitumor evaluations demonstrated that the codelivered nanosphere platform exhibited excellent tumor targeting and synergistic antitumor efficacy.

Improved stability, epithelial permeability and cellular antioxidant activity of ß-carotene via encapsulation by self-assembled α-lactalbumin micelles.

The low aqueous solubility, stability and bioavailability of hydrophobic bioactive compounds, such as ß-carotene (ß-c), greatly hinder their application in foods. Nanocarriers could overcome this problem by facilitating the delivery of the functional ingredients. We prepared lactalbumin (α-lac) micelles by partial enzymatic hydrolysis in aqueous solution. ß-c can be incorporated into the cores of these micelles via hydrophobic interactions. The aqueous solubility and stability under 60 °C heating or UV light irradiation of encapsulated ß-c improved significantly compared with free ß-c. Moreover, it had an increased cellular uptake (3 times) and transmembrane permeability (13 times) in a Caco-2 cell monolayer model. It suggested that α-lac micelle-encapsulated ß-c had an enhanced cellular absorption and transport efficiency. Encapsulated ß-c also exhibited an enhanced cellular anti-oxidant activity (CAA) compared with free ß-c. This work demonstrates that α-lac micelles showed a great potential for delivery of hydrophobic bioactive compounds in foods.

Enzymatically Partially Hydrolyzed α-Lactalbumin Peptides for Self-Assembled Micelle Formation and Their Application for Coencapsulation of Multiple Antioxidants.

The codelivery system for multiple antioxidants such as anthocyanins (Ant) and curcumin (Cur) of synergistic action may effectively enhance their stability and cellular absorption. We have reported that amphiphilic peptides obtained from enzymatic partial hydrolysis of α-lactalbumin (α-lac) can self-assemble into 20 nm monodispersed nanomicelles in aqueous solution. Cur and Ant could be coloaded into the micelles sequentially via hydrophobic and electrostatic interactions, which was proved by fluorescence quenching experiments for the Cur-micelle and Ant-micelle interactions. Circular dichroism spectra proved that the Cur and Ant binding did not affect their structure confirmation. Both Cur- and Ant-loaded micelles showed improved stability and also exhibited an intestinal pH responsive release property in simulated gastrointestinal fluid. In addition, the nanomicelles exhibited an advanced cellular uptake and transmembrane permeability based on Caco-2 cell monolayer models. Finally, the coloaded micelles possessed a synergistic efficiency such that cellular antioxidant activity (CAA) for Cur and Ant was markedly improved.