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We have previously reported that curcumin inhibits urothelial tumor development in a rat bladder carcinogenesis model. In this study, we report that curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway. Curcumin inhibits IGF2 expression at the transcriptional level and decreases the phosphorylation levels of IGF1R and IRS-1 in bladder cancer cells andN-methyl-N-nitrosourea (MNU)-induced urothelial tumor tissue. Ectopic expression of IGF2 and IGF1R, but not IGF1, in bladder cancer cells restored this process, suggesting that IGF2 is a target of curcumin. Moreover, introduction of constitutively active AKT1 abolished the inhibitory effect of curcumin on cell proliferation, migration, and restored the phosphorylation levels of 4E-BP1 and S6K1, suggesting that curcumin functions via suppressing IGF2-mediated AKT/mTOR signaling pathway. In summary, our results reveal that suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway is one of the mechanisms of action of curcumin. Our findings suggest a new therapeutic strategy against human bladder cancer caused by aberrant activation of IGF2, which are useful for translational application of curcumin. [ABSTRACT FROM AUTHOR]

To overcome the side effects and drug resistance in cancer chemotherapy, oxaliplatin (OXA) was encapsulated in chitosan based polymeric micelles with glycolipid-like structure, which were formed by stearic acid-grafted chitosan oligosaccharide (CSO-SA). CSO-SA with 6.89% amino substituted degree was synthesized in this paper. The critical micelle concentration was about 0.12 mg/mL. CSO-SA micelles with the concentration of 1.0 mg/mL had 34.8 nm number average diameter and ++50.8 mV surface potential in the aqueous medium. Thin-film dispersed method mediated by lecithin was chosen to prepare OXA-loaded CSO-SA micelles (CSO-SA/OXA), encapsulation efficiency of which could reach up to about 47%. In vitro anti-tumor activity of CSO-SA/OXA micelles against drug sensitive tumor cells and drug resistant cells was then examined. Using SGC-7901, SKOV3, BEL-7402, K562, and MCF-7 as model drug sensitive tumor cells, the 50% inhibition of cellular growth (IC50) of CSO-SA/OXA micelles could be lowered about 3-6 folds compared to that of free OXA solution. Furthermore, cytotoxicity test of CSO-SA/OXA micelles against MCF-7 and multidrug resistant MCF-7 (MCF-7/Adr) cells presented the reversal activity against MCF-7/Adr cells. The present micelles are a promising carrier candidate for platinum drug to improve the anti-tumor activity. [ABSTRACT FROM AUTHOR]

Chlorines are attractive compounds for photodynamic therapy because of their high absorption in the red wavelength region. The stearic acid–grafted chitosan oligosaccharide (CSO-SA) micelles have been presented as potential candidates for intracellular drug delivery carrier because of their special structure. In this study, CSO-SA micelles were prepared to encapsulate chlorine e6 (Ce6). The physicochemical properties of synthesized CSO-SA micelles were characterized. The critical micelle concentration (CMC) of CSO-SA with 4.96% amino substituted degree (SD %) was about 36.27 ± 1.51 μg/mL. The Ce6-loaded CSO-SA micelles were then prepared by a dialysis method, and the properties and drug release profiles of Ce6-loaded CSO-SA micelles (CSO-SA/Ce6) were investigated. The loading of Ce6 in the CSO-SA micelles could reach higher drug encapsulation efficiency (%), which was ~100%. The size of CSO-SA/Ce6 decreased after the loading of Ce6. The zeta potential of CSO-SA/Ce6 and the drug release rate decreased with the loading content of drug. After the Ce6 molecules were encapsulated into the micelles of CSO-SA, the cellular uptake percentage of Ce6 was much more than that of the free drug. And the cellular uptake percentage of CSO-SA/Ce6 micelles was increased with the incubation time in a short period. [ABSTRACT FROM AUTHOR]