Membrane protein-chimeric liposome-mediated delivery of triptolide for targeted hepatocellular carcinoma therapy.

Triptolide (TPL) is a diterpenoid triepoxide with broad antitumor efficacy, while lack of mechanism of action, severe systemic toxicity, and poor water solubility of TPL limited its usage. To unveil the mechanism of action and improve the pharmaceutical properties of TPL, here we explored the molecular mechanism of TPL and then fabricated TPL-loaded membrane protein-chimeric liposomes (TPL@MP-LP) and tested its anticancer efficacy against hepatocellular carcinoma (HCC). CCK8 assay, colony formation assay, EdU assay, and flow cytometry were used to examine the activity of TPL. RNA sequence and gain-and-loss of function assays were used to explore the molecular mechanisms. TPL@MP-LP was characterized by size, zeta potential, polydispersity index, and transmission electron microscopy. Cellular uptake and cell viability assay were performed to evaluate the internalization and anticancer efficacy of TPL@MP-LP in vitro. Biodistribution and in vivo antitumor efficacy of TPL@MP-LP were evaluated on orthotopic HCC mice models. TPL robustly inhibited HCC cells by inducing cell proliferation arrest, apoptosis via the mitochondrial pathway, and necroptosis via RIPK1/RIPK3/MLKL signaling. TPL was successfully loaded into MP-LP, with a drug-loading capacity of 5.62 ± 0.80%. MP-LP facilitated TPL internalization and TPL@MP-LP exerted enhanced anticancer efficacy against Huh7 cells. TPL@MP-LP showed targeting ability to the tumor site. More importantly, TPL@MP-LP treatment suppressed tumor growth but showed minimal damage to liver and renal functions. TPL exerted anticancer effects on HCC via inducing cell proliferation arrest, apoptosis, and necroptosis, and the MP-LP might be a promising delivery strategy to improve the antitumor efficacy while mitigating toxicity of TPL for HCC therapy.

Long noncoding AFAP1-antisense RNA 1 is upregulated and promotes tumorigenesis in gastric cancer.

Long noncoding RNA serves important roles in gastric cancer (GC). However, the prognostic significance and tumorigenesis effect of AFAP1-antisense RNA 1 (AS1) in GC remain to be clarified. The present study was conducted in order to determine the expression level of AFAP1-AS1 by reverse transcription-quantitative polymerase chain reaction. It was demonstrated that AFAP1-AS1 expression level was higher in GC tissues in comparison with adjacent tissues. By analyzing 66 GC tissue specimens, AFAP1-AS1 expression level was found to be markedly associated with tumor size, clinical stage and differentiation. By performing multivariate Cox regression test, AFAP1-AS1 expression level was confirmed to be an independent factor for poor prognosis in patients with GC. Furthermore, SGC-7901 and BGC-823 cells were used for further investigation following transfection of an AFAP1-AS1 short hairpin RNA lentiviral vector. Knockdown of AFAP1-AS1 significantly inhibited GC cell proliferation, migration and invasion abilities in vitro. Finally, nude mice experiments confirmed that downregulation of AFAP1-AS1 in GC cells suppressed tumor growth in vivo. In conclusion, the results of the present study suggested that AFAP1-AS1 may serve as a valuable prognostic indicator and therapeutic target for GC.

Cytotoxicity of hollow silica nanoparticles loaded with photosensitizes on huh-7 cells.

To observe the cytotoxic effect of the photodynamic therapy mediated by the traditional photosensitizer polyhematoporphyrin (C(34)H(38)N(4)NaO(5), Photosan-II Photosan-II was loaded into HSNP by one-step wet chemical, PS) and hollow silica nanoparticles (HSNP) loaded PS on Huh-7 cells and compare the cytotoxic effects. -based synthetic route. The cellular viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Apoptotic and necrotic cells were measured by flow cytometry. The suitable drug concentrations of free PS and HSNP loaded PS on Huh-7 cells were 20mg/L and 5mg/L respectively, and the suitable incubation time were 4 h and 2 h respectively. Under the same drug concentration, the survival rates of free PS and HSNP loaded PS were 62.46%±1.93% and 6.54%±1.24% <. Under the same drug concentration and incubation time, the total rates of apoptosis necrosis caused by free PS and HSNP loaded PS mediated PDT were respectively 22.00% ± 2.24% and 87.23% ± 2.1% <. PS-loaded HSNP mediated PDT can inhibit proliferation of cancer cells and induce apoptosis more quickly and effectively. As the loading system of PS, HSNP can make the photosensitizer have stronger solubility and drug concentration efficiency, which can significantly improve the therapeutic effect of PDT.

Ornithine decarboxylase and glutamate decarboxylase 65 as prognostic markers of gallbladder malignancy: a clinicopathological study in benign and malignant lesions of the gallbladder.

Ornithine decarboxylase (ODC) plays a critical role in cell proliferation and is overexpressed in a variety of cancers. Furthermore, γ-aminobutyric acid (GABA) content and glutamate decarboxylase (GAD) activity are increased in neoplastic tissues in colon and breast cancer. However, few studies have examined these molecules in gallbladder cancer specimens. We observed the expression levels of ODC and GAD65 in benign and malignant lesions of the gallbladder and investigated their clinicopathological significance for the first time. The expression levels of ODC and GAD65 in specimens from gallbladder adenocarcinoma (n=108), peritumoral tissues (n=46), adenomatous polyps (n=15) and chronic cholecystitis (n=35) were detected using immunohistochemical methods. Kaplan-Meier survival and Cox regression analyses were carried out to explore the clinical and pathological correlations. The levels of positive staining of ODC and GAD65 were significantly higher in gallbladder adenocarcinoma than in peritumoral tissues, adenomatous polyps and chronic cholecystitis. The Kaplan­Meier survival analysis and Cox regression analysis showed that the expression of ODC and GAD65 correlated significantly with the one-year survival rate and the mean survival time of the patients postoperatively. We conclude that the overexpression of ODC and GAD65 are significant in the carcinogenesis and progression of gallbladder adenocarcinoma. They may be important biological markers for the evaluation of biological behaviors and the prognosis of gallbladder adenocarcinoma.