Self-assembly is a powerful means to fabricate multifunctional smart nanotheranostics. However, the complicated preparation, toxicity of responsive carriers, and low loading efficiency of drug cargo hinder the outcome. Herein, we developed a responsive carrier-free noncovalent self-assembly strategy of a metallized Au(III) tetra-(4-pyridyl) porphine (AuTPyP) anticancer drug for the preparation of a heat/acid dual-stimulated nanodrug, and it generated a better photothermal effect than monomers under irradiation. The photothermal effect promoted the protonation of the hydrophobic pyridyl group and the following release into tumorous acidic microenvironments. With cRGD modification, the released drug induced the aggravation of intracellular reactive oxygen species (ROS) via the activity inhibition of thioredoxin reductase (TrxR) for synergistic chemo-photothermal therapy of tumors.
HS1 associated protein X-1 (HAX-1), a substrate of Src family tyrosine kinases, plays a critical role in cell apoptosis. However, its functions in prostate cancer remains unclear. The present study explored the role and mechanism of HAX-1 in cancer cell apoptosis. The mRNA and protein levels of HAX-1 in the prostate cancer cell lines PC-3, VCaP and DU145 were assessed. Cell proliferation, apoptosis and caspase-9 activities were assessed in DU145 after HAX-1 siRNA treatment. The mRNA and protein levels of HAX-1 in prostate cancer cell lines PC-3, VCaP and DU145 were significantly higher than those in the primary prostate epithelial cells, and DU145 possess the highest mRNA and protein levels compared to PC-3 and VCaP. When HAX-1 was knocked down in DU145, cell proliferation was significantly decreased, accompanied by a decrease in Ki67 protein expression. Compared with the control and control siRNA groups, HAX-1 siRNA promoted cell apoptosis and caspase-9 activation in DU145. Furthermore, prostate cancer cells co-transfected with HAX-1 and caspase-9 promoted viability and reduced apoptosis. In contract, co-transfection of caspase-9 and HAX-1 siRNA suppressed the cell viability and enhanced apoptosis. In summary, the present study demonstrated that HAX-1 inhibits cell apoptosis through caspase-9 inactivation.
PFN2 is an invasion promoter in several cancers including lung cancer. However, the probable effects and underlying mechanisms of PFN2 in tumor cell epithelial-mesenchymal-transition (EMT) of non-small cell lung cancer (NSCLC) remain poorly understood. The protein and mRNA levels of PFN2 in human bronchial epithelial cell line 16HBE and three NSCLC cell lines A549, NCI-H520 and 95D were assessed. The gain-of-function (overexpression) and loss‑of-function (siRNA) experiments of PFN2 were performed in 95D cells. A dual-luciferase reporter assay, western blotting and real-time PCR were used to investigate the relationship between PFN2 and miR‑30a‑5p. PFN2 was upregulated in three NSCLC cell lines, and the highest in 95D cell line. Furthermore, the upregulation of PFN2 promoted, whereas the downregulation of PFN2 suppressed invasion and EMT in 95D. Dual-luciferase reporter assay showed that miR‑30a‑5p directly interacts with the 3'-untranslated region (3'-UTR) of PFN2 mRNA. Interestingly, miR‑30a‑5p negatively regulates the expression of PFN2 and suppresses EMT and invasion in 95D. In summary, the present study demonstrated that miR‑30a‑5p inhibits EMT and invasion in high invasive NSCLC cell lines via targeting PFN2. Suggesting the association of miR‑30a‑5p and PFN2 may play an essential role in the development of NSCLC by modulating EMT and cell invasion.
Plasmacytoma variability translocation 1 (PVT1), an oncogene, has been reported to be highly expressed in many tumors, including human glioma, gastric cancer, and non-small cell lung cancer. Functionally, it could also regulate the development of tumor cells. However, its specific roles and pathogenesis in human gliomas are still not clear. This study investigated the function and mechanism of PVT1 knockdown in the proliferation and malignant transformation of human gliomas. We first examined the expression levels of PVT1 and miR-424 in human glioma tissues and cell lines. We also used gene manipulation techniques to explore the effects of PVT1 knockdown on cell viability, migration, invasion, and miR-424. We found that PVT1 knockdown effectively inhibited cell viability, migration, and invasion of human glioma cells and increased miR-424 expression. Based on the negative correlation between PVT1 and miR-424, we then confirmed the direct interaction between PVT1 and miR-424 using RNA immunoprecipitation (RIP) and luciferase reporter assays. Further, we established a xenograft nude mouse model to determine the role and mechanism of PVT1 on tumor growth in vivo. In addition, PVT1 knockdown was shown to promote miR-424 in vivo. In summary, the present study demonstrated that PVT1 knockdown could negatively regulate miR-424 to inhibit human glioma cell activity, migration, and invasiveness. PVT1 knockdown could negatively regulate miR-424 to inhibit cellular activity, migration, and invasiveness in human gliomas, which explained the oncogenic mechanism of PVT1 in human gliomas. It also suggested that PVT1 might be a novel therapeutic target for human gliomas.
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