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mTOR signaling is associated with the clinical pathological parameters of human CRC. siRNA-mediated gene silencing of mTOR may be a novel therapeutic strategy for CRC.

The objective of this study was to evaluate the targeted T1-magnetic resonance imaging (MRI), quantitative biodistribution and toxicity of aptamer (AS411) conjugated Mn3O4@SiO2 core-shell nanoprobes (NPs) in human cervical carcinoma tumor-bearing mice. The NPs were firstly prepared by encapsulating a hydrophobic Mn3O4 core within an amino functionalized silica shell. The fluorophore rhodamine (RB) was doped into the silica shell and the amphiphilic polymer poly(ethylene glycol) (PEG) was modified on the surface of the shell to improve its biocompatibility, then the aptamer AS411 was conjugated onto the end of the PEG chains as targeting ligands. The final NPs were abbreviated as Mn3O4@SiO2(RB)-PEG-Apt. By means of in vitro fluorescence confocal imaging and in vivo MRI, the NPs have been demonstrated to target cancer cells and prominent tumor aggregation effectively. The imaging results were further confirmed by a quantitative biodistribution study. In addition, histological, hematological and biochemistry analysis also proved the low toxicity of NPs in vivo. Our results showed the great potential of the Mn3O4@SiO2(RB)-PEG-Apt NPs could be used as a multifunctional nanoplatform for long-term targeted imaging and therapy of cancer.

BackgroundOridonin, a tetracycline diterpenoid compound, has the potential antitumor activities. Here, we evaluate the antitumor activity and action mechanisms of oridonin in colorectal cancer.MethodsEffects of oridonin on cell proliferation were determined by using a CCK-8 Kit. Cell cycle distribution was determined by flow cytometry. Apoptosis was examined by analyzing subdiploid population and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Senescent cells were determined by senescence-associated β-galactosidase activity analysis. Semi-quantitative RT-PCR was used to examine the changes of mRNA of p16, p21, p27 and c-myc. The concomitant changes of protein expression were analyzed with Western blot. Expression of AcH3 and AcH4 were examined by immunofluorescence staining and Western blots. Effects of oridonin on colony formation of SW1116 were examined by Soft Agar assay. The in vivo efficacy of oridonin was detected using a xenograft colorectal cancer model in nude mice.ResultsOridonin induced potent growth inhibition, cell cycle arrest, apoptosis, senescence and colony-forming inhibition in three colorectal cancer cell lines in a dose-dependent manner in vitro. Daily i.p. injection of oridonin (6.25, 12.5 or 25 mg/kg) for 28 days significantly inhibited the growth of SW1116 s.c. xenografts in BABL/C nude mice. With western blot and reverse transcription-PCR, we further showed that the antitumor activities of oridonin correlated with induction of histone (H3 and H4) hyperacetylation, activation of p21, p27 and p16, and suppression of c-myc expression.ConclusionOridonin possesses potent in vitro and in vivo anti-colorectal cancer activities that correlated with induction of histone hyperacetylation and regulation of pathways critical for maintaining growth inhibition and cell cycle arrest. Therefore, oridonin may represent a novel therapeutic option in colorectal cancer treatment.

Tumor immune escape is an important part of tumorigenesis and development. Tumor cells can develop a variety of immunosuppressive mechanisms to combat tumor immunity. Exploring tumor cells that escape immune surveillance through the molecular mechanism of related immunosuppression in-depth is helpful to develop the treatment strategies of targeted tumor immune escape. The latest studies show that CD24 on the surface of tumor cells interacts with Siglec-10 on the surface of immune cells to promote the immune escape of tumor cells. It is necessary to comment on the molecular mechanism of inhibiting the activation of immune cells through the interaction between CD24 on tumor cells and Siglec-10 on immune cells, and a treatment strategy of tumors through targeting CD24 on the surface of tumor cells or Siglec-10 on immune cells.