Propofol is one of the extensively commonly used intravenous anesthetic agents. Previous studies have indicated that propofol has the ability to influence the biological behavior of several human cancer cells. However, the effect of propofol on osteosarcoma and its related molecular mechanisms are still not clear. Here we found that propofol significantly elevated the expression of miR-143, inhibited cell proliferation and invasion, and promoted apoptosis in osteosarcoma cell line MG63. Propofol also efficiently decreased protein expression of matrix metalloproteinase 13 (MMP-13). Moreover, the overexpression of miR-143 decreased MMP-13 protein level. Finally, the neutralization of miR-143 by anti-miR-143 antibody reversed the effect of propofol on cell proliferation, apoptosis, and invasion and upregulated MMP-13 expression in MG63 cells. Taken together, propofol may have antitumor potential in osteosarcoma, which is partly due to the downregulation of MMP-13 expression by miR-143.
OBJECTIVE:The aim of this study was to investigate the serum level of microRNA (miR)-21 in patients with osteosarcoma and its correlation with chemosensitivity and prognosis. METHODS: miR-21 levels in sera from 65 patients with osteosarcoma and 30 healthy controls were measured by real-time reverse transcription-polymerase chain reaction. Correlations between serum miR-21 and clinicopathological features in patients with osteosarcoma were determined. The prognostic significance of serum miR-21 was assessed using a Cox proportional hazards model. RESULTS: The serum level of miR-21 was significantly higher in patients with osteosarcoma than in control subjects. High serum miR-21 was significantly correlated with advanced Enneking stage and chemotherapeutic resistance. Univariate and multivariate analyses for overall survival showed that upregulation of serum miR-21 was an independent, unfavourable prognostic factor for patients with osteosarcoma (hazard ratio, 2.325). CONCLUSIONS: miR-21 might be a good candidate for a therapeutic target, and a potential biomarker for the prediction of chemotherapeutic sensitivity and prognosis in patients with osteosarcoma.
Currently, phototherapy initiated by local irradiation with a near-infrared (NIR) laser has emerged as a promising strategy for cancer treatment owing to its low toxicity. However, a key problem for effective phototherapy is how to specifically deliver a sufficient dose of photosensitizers to a tumor focus. Herein, indocyanine green (ICG), a United States Food and Drug Administration (US FDA)-approved photosensitizer, was first encapsulated in an inner aqueous compartment of liposome (ICG-LIP) to improve its stability. Thereafter, tumor cell membranes were isolated from native glioma cells and subsequently inlaid in the bilayer lipid membrane of ICG-LIP to construct cell-like liposomes (ICG-MCLs). ICG was easily encapsulated into the ICG-MCLs with a very high encapsulation efficiency, reaching 78.01 ± 0.72% and its concentration in the final formulation reached 200 μg mL-1. The ICG-MCLs displayed a spherical morphology with a hydrodynamic diameter (Dh) of 115.0 ± 0.5 nm, a PDI of 0.14, and a zeta potential of -11.2 ± 0.9 mV. Moreover, ICG-MCLs exhibited a good stability in terms of particle size and significantly improved the chemical stability of ICG in pH 7.4 PBS at 37 °C. In addition, the temperature of the ICG-MCLs rapidly increased to 63 °C after 10 min irradiation and this was maintained for a longer time. Owing to the cancer cell membrane associated protein, the ICG-MCLs were specifically internalized by homogenous glioma C6 cells in vitro, which resulted in the strong red fluorescence of ICG in cytoplasm. Moreover, in vivo imaging showed that the ICG-MCLs were effectively homed to the tumor site of C6 glioma-bearing Xenograft nude mice through vein injection, which resulted in the temperature of the tumor site rapidly rising, allowing the killing of tumor cells after local NIR irradiation. After treatment with the ICG-MCLs, the primary tumor focus was completely eradicated and lung metastases were effectively inhibited. In conclusion, liposomes inlaid with tumor cellular membranes may serve as an excellent nanoplatform for homologous-targeting phototherapy using ICG.
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