CuS-MnS2 nano-flowers for magnetic resonance imaging guided photothermal/photodynamic therapy of ovarian cancer through necroptosis.

With a high incidence and high mortality rate, ovarian cancer presents a challenge for clinical practice. It is thus extremely urgent to investigate new diagnosis and therapy methods for the treatment of ovarian cancer. Ternary copper-based chalcogenide nanomaterials are attractive owing to their near infrared (NIR) response for cancer theranostic fields. However, improving the theranostic efficiency of these nanomaterials is challenging. Herein, CuS-MnS2 nano-flowers were easily synthesized and under NIR irradiation exhibited a relatively high photothermal conversion efficiency of 67.5% and a simultaneous reactive oxygen species (ROS) generation effect. Owing to these outstanding photothermal/photodynamic effects, excellent tumor ablation results could be achieved by the combined use of CuS-MnS2 nano-flowers and 808 nm NIR laser treatments. The main anticancer mechanism of CuS-MnS2 nano-flowers + NIR was likely necroptosis. In addition, the nano-flowers showed remarkable contrast enhancement according to magnetic resonance imaging (MRI). These CuS-MnS2 nano-flowers could thus serve as a promising multifunctional nanotheranostic agent for MRI and as a photothermal/photodynamic cancer therapy agent through necroptosis.

A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response.

The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two-stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT-PCR analysis (qRT-PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10-19 ). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC.

Berberine Increases Doxorubicin Sensitivity by Suppressing STAT3 in Lung Cancer.

Berberine (BBR), an alkaloid component isolated from Chinese medicinal herb Huang Lian, has aroused broad interests for its antitumor effect in recent years. The signal transducer and activator of transcription 3 (STAT3), plays critical roles in malignant transformation and progression and was found to be constitutively activated in a variety of human cancers. In this study, we show that BBR inhibited cell proliferation, induced apoptosis, and suppressed tumor spheroid formation of lung cancer cell lines. These effects were correlated with BBR-mediated suppression of both phosphorylated and total levels of STAT3 protein. Furthermore, BBR promoted STAT3 degradation by enhancing ubiquitination. Importantly, we demonstrated that BBR was able to inhibit doxorubicin (DOX)-mediated STAT3 activation and sensitize lung cancer cells to the cytotoxic effect of DOX treatment. Given that BBR is widely used in clinic with low toxicity, our results are potentially important for the development of a novel combinatorial therapy with BBR and DOX in the treatment of lung cancer.

Effects of epigallocatechin gallate on the proliferation and apoptosis of the nasopharyngeal carcinoma cell line CNE2.

The present study explored the effects of epigallocatechin gallate (EGCG) on the cell cycle, proliferation and apoptosis of the nasopharyngeal carcinoma cell line CNE2 in vitro. The proliferation of CNE2 cells was detected using the cell counting kit-8 method. Cell cycle distribution and apoptosis were detected using flow cytometry. The human telomerase reverse transcriptase (hTERT) mRNA expression was determined using reverse transcription polymerase chain reactions. The protein expression of hTERT and Myc proto-oncogene protein (c-Myc) was observed using western blot analysis. EGCG inhibited the proliferation of CNE2 cells in a concentration-dependent manner (P<0.05) and blocked the cell cycle progression of the cells. In the low concentration (100 µg/ml) group, the cell cycle arrest showed a time-dependent manner. However, as the concentration increased and action time was prolonged, this time dependency became less marked. EGCG promoted the apoptosis of CNE2 cells in a time-dependent manner. In addition, EGCG downregulated the mRNA and protein expression of hTERT and downregulated the expression of c-Myc protein. Downregulation of the expression of hTERT and c-Myc was more evident in the high-dose group (200 µg/mL). In conclusion, EGCG has proliferation-inhibiting, cell cycle-blocking and apoptosis-promoting effects on CNE2 cells. EGCG may be developed into an auxiliary therapeutic agent for the treatment of nasopharyngeal carcinoma.

Effects of different concentrations of amino acids in the culture medium on preimplantation mouse embryo development in vitro.

OBJECTIVE: To evaluate the effects of amino acids (AA) on the development of in vitro cultured preimplantation embryos of Kunming mice, and define the optimal AA concentration for embryo culture. METHODS: Totally 630 zygotes were collected from the oviducts of superovulated female Kunming mice, which were cultured in protein-free potassium simplex optimized medium (mKSOM) supplemented with Eagle's essential amino acids and Eagle's non-essential amino acids of different concentrations (mKSOM, mKSOM+1/16AA, mKSOM+1/8AA, mKSOM+1/4AA, mKSOM+1/2AA, mKSOM+AA, and mKSOM+2AA). RESULTS: The embryos cultured with the amino acids showed higher development rate to both 8-cell embryo stage and blastocyst stage than those cultured without amino acids. The correlation of amino acid concentration with 8-cell and blastocyst development rates conformed to the cubic model, with the highest development rate to both of the two stages observed at half of the amino acid concentration. CONCLUSION: Amino acids can promote the development of preimplantation Kunming mouse embryos, but excessively high concentration of amino acids impair embryo development possibly because of metabolic and osmotic pressure changes of the embryos as well as toxicity of ammonium resulting from the metabolism of amino acids.