Expression and prognostic role of PANK1 in glioma.

Background Malignant gliomas are the most common type of primary malignant brain tumors. Pantothenate kinase 1 (PANK1) mRNA is highly expressed in several metabolic processes, implying that PANK1 plays a potential role in metabolic programming in cancers. However, the role of PANK1 in glioma has not been fully explored. Methods Public datasets (The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Gravendeel and Rembrandt) and validation cohort were used to explore the expression of PANK1 in glioma tissues. Kaplan-Meier and Cox regression analyses were used to explore the relationship between PANK1 and prognosis in glioma. Cell proliferation and invasion were determined using Cell Counting Kit-8 (CCK8) and transwell invasion in vitro assays. Results Analysis using the four public datasets and the validation cohort showed that PANK1 expression was significantly downregulated in glioma tissues compared with non-tumor tissues (P<0.01). PANK1 expression was negatively correlated with World Health Organization (WHO) grade, 1p/19q non-codeletion and isocitric dehydrogenase 1/2 (IDH1/2) wildtype. Furthermore, high expression of PANK1 was correlated with significantly better prognosis of glioma patients compared to patients with low expression of PANK1 (all P<0.01 in the four datasets). Besides, both lower-grade glioma (LGG) and glioblastoma multiform (GBM) patients with high expression of PANK1 had a significantly better prognosis than those with low expression of PANK1 in TCGA, Gravendeel and Rembrandt datasets (all P <0.01). Multivariate Cox regression analysis revealed that low PANK1 expression was an independent risk factor associated with a worse prognosis of glioma patients. Moreover, overexpression of PANK1 significantly inhibited the proliferation and invasion of U87 and U251 cells. Conclusion PANK1 expression is downregulated in glioma tissues and is a novel prognostic biomarker in glioma patients.

Erratum: MUC3A promotes non-small cell lung cancer progression via activating the NFκB pathway and attenuates radiosensitivity.

[This corrects the article DOI: 10.7150/ijbs.59430.].

Modified chemical reaction optimization and its application in engineering problems.

Chemical Reaction Optimization (CRO) is a simple and efficient evolutionary optimization algorithm by simulating chemical reactions. As far as the current research is concerned, the algorithm has been successfully used for solving a number of real-world optimization tasks. In our paper, a new real encoded chemical reaction optimization algorithm is proposed to boost the efficiency of the optimization operations in standard chemical reactions optimization algorithm. Inspired by the evolutionary operation of the differential evolution algorithm, an improved search operation mechanism is proposed based on the underlying operation. It is modeled to further explore the search space of the algorithm under the best individuals. Afterwards, to control the perturbation frequency of the search strategy, the modification rate is increased to balance between the exploration ability and mining ability of the algorithm. Meanwhile, we also propose a new population initialization method that incorporates several models to produce high-quality initialized populations. To validate the effectiveness of the algorithm, nine unconstrained optimization algorithms are used as benchmark functions. As observed from the experimental results, it is evident that the proposed algorithm is significantly better than the standard chemical reaction algorithm and other evolutionary optimization algorithms. Then, we also apply the proposed model to address the synthesis problem of two antenna array synthesis. The results also reveal that the proposed algorithm is superior to other approaches from different perspectives.

MUC3A promotes non-small cell lung cancer progression via activating the NFκB pathway and attenuates radiosensitivity.

Mucin 3A (MUC3A) is highly expressed in non-small cell lung cancer (NSCLC), but its functions and effects on clinical outcomes are not well understood. Tissue microarray of 92 NSCLC samples indicated that high levels of MUC3A were associated with poor prognosis, advanced staging, and low differentiation. MUC3A knockdown significantly suppressed NSCLC cell proliferation and induced G1/S accumulation via downregulating cell cycle checkpoints. MUC3A knockdown also inhibited tumor growth in vivo and had synergistic effects with radiation. MUC3A knockdown increased radiation-induced DNA double strain breaks and γ-H2AX phosphorylation in NSCLC cells. MUC3A downregulation inhibited the BRCA-1/RAD51 pathway and nucleus translocation of P53 and XCRR6, suggesting that MUC3A promoted DNA damage repair and attenuated radiation sensitivity. MUC3A knockdown also resulted in less nucleus translocation of RELA and P53 in vivo. Immunoprecipitation revealed that MUC3A interacted with RELA and activated the NFκB pathway via promoting RELA phosphorylation and interfering the binding of RELA to IκB. Our studies indicated that MUC3A was a potential oncogene and associated with unfavorable clinical outcomes. NSCLC patients with a high MUC3A level, who should be more frequent follow-up and might benefit less from radiotherapy.

MUC3A induces PD-L1 and reduces tyrosine kinase inhibitors effects in EGFR-mutant non-small cell lung cancer.

The immune checkpoint ligand programmed death-ligand 1 (PD-L1) and the transmembrane mucin (MUC) 3A are upregulated in non-small cell lung cancer (NSCLC), contributing to the aggressive pathogenesis and poor prognosis. Here, we report that knocking down the oncogenic MUC3A suppresses the PD-L1 expression in NSCLC cells. MUC3A is a potent regulator of epidermal growth factor receptor (EGFR) stability, and MUC3A deficiency downregulates the activation of the PI3K/Akt and MAPK pathways, which subsequently reduces the expression of PD-L1. Furthermore, knockdown of MUC3A and tyrosine kinase inhibitors (TKIs) in EGFR-mutant NSCLC cells play a synergistic effect on inhibited proliferation and promoted apoptosis in vitro. In the BALB/c nude mice xenograft model, MUC3A deficiency enhances EGFR-mutated NSCLC sensitivity to TKIs. Our study shows that transmembrane mucin MUC3A induces PD-L1, thereby promoting immune escape in NSCLC, while downregulation of MUC3A enhances TKIs effects in EGFR-mutant NSCLC. These findings offer insights into the design of novel combination treatment for NSCLC.

Agrin Promotes Non-Small Cell Lung Cancer Progression and Stimulates Regulatory T Cells via Increasing IL-6 Secretion Through PI3K/AKT Pathway.

Non-small cell lung cancer (NSCLC) has high mortality rates worldwide. Agrin contributes to immune synapse information and is involved in tumor metastasis. However, its roles in NSCLC and tumor immune microenvironment remain unclear. This study examined the effects and the underlying mechanisms of Agrin in NSCLC and tumor-infiltrated immune cells. Clinical tissue samples were used to confirm the bioinformatic predictions. NSCLC cells were used to investigate the effects of Agrin on cell cycle and proliferation, as well as invasion and migration. Tumor xenograft mouse model was used to confirm the effects of Agrin on NSCLC growth and tumor-infiltrated regulatory T cells (Tregs) in vivo. Agrin levels in NSCLC cells were closely related to tumor progression and metastasis, and its function was enriched in the PI3K/AKT pathway. In vitro assays demonstrated that Agrin knockdown suppressed NSCLC cell proliferation and metastasis, while PI3K/AKT activators reversed the inhibitory effects of Agrin deficiency on NSCLC cell behaviors. Agrin expression was negatively associated with immunotherapy responses in NSCLC patients. Agrin knockdown suppressed Tregs, as well as interleukin (IL)-6 expression and secretion, while PI3K/AKT activators and exogenous IL-6 rescued the inhibitory effects. In the mouse model, Agrin downregulation alleviated NSCLC cell growth and Treg infiltration in vivo. Our results indicated that Agrin promotes tumor cell growth and Treg infiltration via increasing IL-6 expression and secretion through PI3K/AKT pathway in NSCLC. Our studies suggested Agrin as a therapeutically potential target to increase the efficacy of immunotherapy in NSCLC patients.

MFP-FePt-GO Nanocomposites Promote Radiosensitivity of Non-Small Cell Lung Cancer Via Activating Mitochondrial-Mediated Apoptosis and Impairing DNA Damage Repair.

Background: Recent advances in nanomedicine provided promising alternatives for tumor treatment to improve the survival and life quality of cancer patients. This study was designed to explore the insight mechanisms of the anti-tumor effects of the novel nanocomposites (NCs) MFP-FePt-GO with non-small cell lung cancer (NSCLC). Methods: A chemical co-reduction method was applied to the synthesis process of MFP-FePt-GO NCs. The chemical synthesis efficiency and morphology of the NCs were measured with spectroscope and transmission electron microscope. Colony formation assay and cell apoptosis were conducted to assess the radiosensitivity effect of NCs with radiation. Then, we detected cell mitochondrial membrane potential and reactive oxygen species (ROS) level by flow cytometry to further explore the cause of cell death. Immunofluorescence staining and Confocal were carried out to determine the DNA damage repair. A Lewis lung carcinoma animal model was used to measure safety and anti-tumor efficiency in vivo. Results: The novel NCs MFP-FePt-GO designed on a lamellar-structure magnetic graphene oxide and polyethylene glycol drug delivery system was synthesized and functionalized for co-delivery of metronidazole and 5-fluorouracil. While no severe allergies, liver and kidney damage, or drug-related deaths were observed, MFP-FePt-GO NCs promoted radiosensitivity of NSCLC cells both in vivo and in vitro. It improved the effects of radiation via activating intrinsic mitochondrial-mediated apoptosis and impairing DNA damage repair. This NCs also induced a ROS burst, which suppressed the antioxidant protein expression and induced cell apoptosis. Furthermore, MFP-FePt-GO NCs prevented NSCLC cell migration and invasion. Conclusion: MFP-FePt-GO NCs showed a synergistic anti-tumor effect with radiation to eliminate tumors. With good safety and efficacy, this novel NCs could be a potential radiosensitive agent for NSCLC patients.

Downregulation of Nitric Oxide Collaborated with Radiotherapy to Promote Anti-Tumor Immune Response via Inducing CD8+ T Cell Infiltration.

The production of nitric oxide (NO) is a key feature of immunosuppressive myeloid cells, which impair T cell activation and proliferation via reversibly blocking interleukin-2 receptor signaling. NO is mainly produced from L-arginine by inducible NO synthase (iNOS). Moreover, L-arginine is an essential element for T cell proliferation and behaviors. Impaired T cell function further inhibits anti-tumor immunity and promotes tumor progression. Previous studies indicated that radiotherapy activated anti-tumor immune responses in multiple tumors. However, myeloid-derived cells in the tumor microenvironment may neutralize these responses. We hypothesized that iNOS, as an important regulator of the immunosuppressive effects in myeloid-derived cells, mediated radiation resistance of cancer cells. In this study, we used 1400W dihydrochloride, a potent small-molecule inhibitor of iNOS, to explore the regulatory roles of NO in anti-tumor immunity. Radiotherapy and iNOS inhibition by 1400W collaboratively suppressed tumor growth and increased survival time, as well as increased tumor-infiltrating CD8+ T cells and specific inflammatory cytokine levels, in both lung and breast cancer cells in vivo. Our results also suggested that myeloid cell-mediated inhibition of T cell proliferation was effectively counteracted by radiation and 1400W-mediated NO blockade in vitro. Thus, these results demonstrated that iNOS was an important regulator of radiotherapy-induced antitumor immune responses. The combination of radiotherapy with iNOS blockade might be an effective therapy to improve the response of tumors to clinical radiation.

Molecular Interactions for the Curcumin-Polymer Complex with Enhanced Anti-Inflammatory Effects.

The molecular interactions between compound and polymeric carriers are expected to highly contribute to high drug load and good physical stability of solid dispersions. In this study, a series of amorphous solid dispersions (ASD) of Curcumin (Cur) were prepared with different polymers by the solvent evaporation method. With the carrier polyvinylpyrrolidone (PVP), the amorphous solid dispersion system exhibits a better solubility and stability than that with poloxamers and HP-ß-CD due to the strong drug-polymer interaction. The drug/polymer interaction and their binding sites were investigated by combined experimental (XRD, DSC, FTIR, SEM, Raman, and 1H-NMR) and molecular dynamics simulation techniques. The Curcumin ASD demonstrated enhanced bioavailability by 11-fold and improved anti-inflammatory activities by the decrease in cytokine production (MMP-9, IL-1ß, IL-6, VEGF, MIP-2, and TNF-α) compared to the raw Curcumin. The integration of experimental and modeling techniques is a powerful tool for the rational design of formulation development.

Development of a hypoxic nanocomposite containing high-Z element as 5-fluorouracil carrier activated self-amplified chemoradiotherapy co-enhancement.

The synergetic effect of chemoradiotherapy achievement is encouraging but significantly hampered by the prevalence of hypoxia, leading to drug/radiation resistance in solid tumours. To address the problem and improve the efficiency of cancer therapy, a lamellar-structure multifunctional graphene oxide (GO) drug-delivery system with an average size of 243 nm, co-delivering of metronidazole (MI), 5-fluorouracil (5-FU) and FePt magnetic nanoparticles (MNPs), was successfully designed and synthesized in the study. The integration of hypoxic drug carrier loading radiosensitizers and chemotherapeutic drugs simultaneously, combines the properties of hypoxia-sensitivity and chemoradiotherapy co-enhancement within a single nanoplatform, which is expected to provide new ideas for cancer treatment. Through in vitro tests, the hypoxia-sensitivity and cytotoxicity of intracellular reactive oxygen species (ROS) of the nanocomposites (NCs) were proved. Moreover, the additive effect between MI, 5-FU and FePt MNPs in cytotoxicity and radiation sensitization aspects is disclosed. It performs an enhanced cell proliferation inhibition and makes up a self-amplified radiotherapy enhancement system that improves radiation efficiency and cell radiosensitivity simultaneously. In conclusion, the study recommended a novel and promising multifunctional nanoplatform which performed a self-amplified effect that activated chemoradiotherapy co-enhancement.

Small Nucleolar RNA 71A Promotes Lung Cancer Cell Proliferation, Migration and Invasion via MAPK/ERK Pathway.

Objective: Increasing evidence suggested that dysregulated small nucleolar RNAs (snoRNAs) were involved in tumor development. The roles of snoRNA 71A (SNORA71A) in the progression of non-small cell lung cancer (NSCLC) remained unclear. Methods: Dataset GSE19188 from Gene Expression Omnibus (GEO) database was downloaded to detect the expression levels of SNORA71A in NSCLC tissues. The biological significance of SNORA71A was explored by loss-of-function analysis both in vitro and in vivo. Results: SNORA71A was overexpressed in NSCLC tissues compared with normal tissues, and upregulated SNORA71A was significantly associated with worse survival of NSCLC patients. Knockdown of SNORA71A suppressed proliferation of both A549 and PC9 cells, and induced G0/G1 phase arrest. Knockdown of SNORA71A also suppressed xenograft tumor growth in mice. In addition, knockdown of SNORA71A inhibited cell invasion and migration and suppressed epithelial-mesenchymal transition. Furthermore, downregulated SNORA71A decreased the phosphorylation of MEK and ERK1/2 in the MAPK/ERK signal pathway. Conclusion: SNORA71A functions as an oncogene in NSCLC and may serve as a therapeutic target and promising prognostic biomarker of NSCLC.

FePt/GO Nanosheets Suppress Proliferation, Enhance Radiosensitization and Induce Autophagy of Human Non-Small Cell Lung Cancer Cells.

With the advancement of nanotechnology, various nanocomposites have been applied in the diagnostics and treatment of cancer. We synthetized FePt nanoparticles which were assembled on the surface of graphene oxide (GO). These novel FePt/GO nanosheets simultaneously act as a chemotherapy drug and enhance radiosensitivity. In this study, transmission electron microscope, dynamic light scattering, X-ray photoelectron spectroscope and Fourier transform infrared spectroscopy were used to characterize surface morphology and chemical composition of FePt/GO nanosheets (NSs). Their cytotoxicity in various cancer and normal cells was evaluated by cell counting kit-8 assay, and their effects on radiosensitization were determined by colony formation assay. To explore the underlying mechanisms, we measured the intracellular reactive oxygen species levels and autophagy formation. Monodansylcadaverine-staining, Western Blotting and ultrastructure analysis were utilized to assess autophagy. The results demonstrated that FePt/GO NSs not only selectively suppressed the proliferation of cancer cells, but also increased their radiosensitization. Moreover, FePt/GO NSs induced autophagy, which might result in promoted sensibilization of radiotherapy. In conclusion, with good safety and efficacy, FePt/GO NSs are safe and effective to suppress proliferation, enhance radiosensitization and induce autophagy of human non-small cell lung cancer cells. They are potential for the treatment of lung cancer.

Impact of Radiotherapy Concurrent with Anti-PD-1 Therapy on the Lung Tissue of Tumor-Bearing Mice.

Pneumonitis is a common adverse effect found in non-small cell lung cancer patients after radiotherapy or immune checkpoint inhibitor treatment. We investigated the effects of these two therapies, combined, in the lung tissue of an orthotopic tumor-bearing mouse model. The mice received an 8 Gy dose three times with or without 200 µg anti-programmed death-1 (anti-PD-1) antibody intraperitoneal injection every three days. Lung tissues were H&E stained to determine histological changes. The serum levels of cytokines, such as interferon-γ, tumor necrosis factor and interleukin-5, were detected by cytometric bead array. The neutrophil infiltration was evaluated by immunohistochemical staining for myeloperoxidase. The lung injury score was higher in the treated groups than the control group, especially in the combined treatment group, in which the proportion of neutrophils in lung tissues was significantly higher compared to any other groups. Similarly, the CD4/CD8 ratio of the lung tissues in the combined treatment group, as well as the serum levels of interferon-γ, tumor necrosis factor and interleukin-5, were significantly higher than the other groups. These findings indicate that radiation combined with anti-PD-1 treatment leads to more severe lung injury in the orthotopic tumor-bearing mouse model, accompanied by increased neutrophil infiltration and increased inflammatory response.

Recent Progress of Nanoscale Metal-Organic Frameworks in Cancer Theranostics and the Challenges of Their Clinical Application.

The growing incidence of cancer raises an urgent need to develop effective diagnostic and therapeutic strategies. With the rapid development of nanomedicine, nanoscale metal-organic frameworks (NMOFs) presented promising potential in various biomedical applications in the last 2 decades, especially in cancer theranostics. Due to the unique features of NMOFs, including structural diversities, enormous porosity, multifunctionality and biocompatibility, they have been widely used to deliver imaging contrast agents and therapeutic drugs. Moreover, multiple types of contrast agents, anti-cancer drugs and targeting ligands could be co-delivered through one single NMOF to enable combination therapy. Co-delivering system using NMOFs helped to avoid multidrug resistance, to reduce adverse effects, to achieve imaging-guided precise therapy and to enhance anti-cancer efficacy. This review summarized the recent research advances on the application of NMOFs in biomedical imaging and cancer treatments in the last few years. The current challenges that impeding their translation to clinical practices and the perspectives for their future applications were also highlighted and discussed.

Protective Role of Nuclear Factor-Erythroid 2-Related Factor 2 Against Radiation-Induced Lung Injury and Inflammation.

Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy. Inflammatory cell infiltration, imbalance of inflammatory cytokines, and oxidative damage were reported to be involved during RILI pathogenesis, especially in the early phase of RILI. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidative cascades, and regulates life span of mice after administration of thoracic irradiation. We investigated the effects of Nrf2 on RILI and inflammation using Nrf2-knockout, Nrf2-overexpression and wild-type mice with or without 15 Gy ionizing radiation to thorax. Our results showed that Nrf2 deficiency aggravated radiation-induced histopathological changes, macrophage and neutrophil infiltration, serum levels of pro-inflammatory cytokines (IL-6, MCP-1, IFN-γ, TNF, and IL-12p70), and the levels of peroxidation products in the mouse lung. Moreover, loss of Nrf2 reduced radiation-induced serum levels of anti-inflammatory cytokine, IL-10, and antioxidative proteins. Nrf2 overexpression significantly alleviated radiation-induced histopathological changes, macrophages and neutrophils infiltration, serum levels of pro-inflammatory cytokines, and the levels of peroxidation products in lung tissues. Nrf2 overexpression also increased the serum levels of IL-10 and antioxidative proteins. These results indicated that Nrf2 had a protective role against radiation-induced acute lung injury and inflammation, and that antioxidative therapy might be a promising treatment for RILI.

Trichosanthin enhances sensitivity of non-small cell lung cancer (NSCLC) TRAIL-resistance cells.

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has a specific antitumour activity against many malignant tumours. However, more than half of lung cancer cells are resistant to TRAIL-relevant drugs. Trichosanthin (TCS) is a traditional Chinese medicine with strong inhibitive effects on various malignancies. Nevertheless, its function on TRAIL resistance has not been revealed in non-small cell lung cancer (NSCLC). To examine the molecular mechanisms of TCS-induced TRAIL sensitivity, we administrated TCS to TRAIL-resistance NSCLC cells, and found that the combination treatment of TCS and TRAIL inhibited cancer cell proliferation and invasion, and induced cell apoptosis and S-phase arrest. This combined therapeutic method regulated the expression levels of extrinsic apoptosis-associated proteins Caspase 3/8 and PARP; intrinsic apoptosis-associated proteins BCL-2 and BAX; invasion-associated proteins E-cadherin, N-cadherin, Vimentin, ICAM-1, MMP-2 and MMP-9; and cell cycle-associated proteins P27, CCNE1 and CDK2. Up-expression and redistribution of death receptors (DRs) on the cell surface were also observed in combined treatment. In conclusion, our results indicated that TCS rendered NSCLC cells sensitivity to TRAIL via upregulating and redistributing DR4 and DR5, inducing apoptosis, and regulating invasion and cell cycle related proteins. Our results provided a potential therapeutic method to enhance TRAIL-sensitivity.

FePt-Cys nanoparticles induce ROS-dependent cell toxicity, and enhance chemo-radiation sensitivity of NSCLC cells in vivo and in vitro.

FePt-Cys nanoparticles (FePt-Cys NPs) have been well used in many fields, despite their poor solubility and stability. We synthetized a cysteine surface modified FePt NPs, which exhibited good solubility, stability and biocompatibility. We explored the insight mechanisms of the antitumor effects of this new nanoparticle system in lung cancer cells. In the in vitro study, FePt-Cys NPs induced a reactive oxygen species (ROS) burst, which suppressed the antioxidant protein expression and induced cell apoptosis. Furthermore, FePt-Cys NPs prevented the migration and invasion of H1975 and A549 cells. These changes were correlated with a dramatic decrease in MMP-2/9 expression and enhanced the cellular attachment. We demonstrated that FePt-Cys NPs promoted the effects of chemo-radiation through activation of the caspase system and impairment of DNA damage repair. In the in vivo study, no severe allergies or drug-related deaths were observed and FePt-Cys NPs showed a synergistic effect with cisplatin and radiation. In conclusion, with good safety and efficacy, FePt-Cys NPs could therefore be potential sensitizers for chemoradiotherapy.

Evolving Spatial Clusters of Genomic Regions From High-Throughput Chromatin Conformation Capture Data.

High-throughput chromosome-conformation-capture (Hi-C) methods have revealed a multitude of structural insights into interphase chromosomes. In this paper, we elucidate the spatial clusters of genomic regions from Hi-C contact maps by formulating the underlying problem as a global optimization problem. Given its nonconvex objective and nonnegativity constraints, we implement several evolutionary algorithms and compare their performance with non-negative matrix factorization, revealing novel insights into the problem. In order to obtain robust and accurate spatial clusters, we propose and describe a novel hybrid differential evolution algorithm called HiCDE, which adopts non-negative matrix factorization as local search according to each candidate individual provided by differential evolution algorithm. Based on the fitness value of each individual, the population is partitioned into three subpopulations with different sizes; each subpopulation is equipped with a specific mutation strategy for either exploitation or exploration. Finally, all control parameters in the pool have equal probability to be selected for generating trial vectors. The effectiveness and robustness of HiCDE are supported by real-world performance benchmarking on chromosome-wide Hi-C contact maps of yeast and human, time complexity analysis, convergence analysis, parameter analysis, and case studies.

Biosynthesis, Antibacterial Activity and Anticancer Effects Against Prostate Cancer (PC-3) Cells of Silver Nanoparticles Using Dimocarpus Longan Lour. Peel Extract.

Metal nanoparticles, particularly silver nanoparticles (AgNPs), are developing more important roles as diagnostic and therapeutic agents for cancers with the improvement of eco-friendly synthesis methods. This study demonstrates the biosynthesis, antibacterial activity, and anticancer effects of silver nanoparticles using Dimocarpus Longan Lour. peel aqueous extract. The AgNPs were characterized by UV-vis absorption spectroscopy, X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), and Fourier transform infrared spectroscope (FTIR). The bactericidal properties of the synthesized AgNPs were observed via the agar dilution method and the growth inhibition test. The cytotoxicity effect was explored on human prostate cancer PC-3 cells in vitro by trypan blue assay. The expressions of phosphorylated stat 3, bcl-2, survivin, and caspase-3 were examined by Western blot analysis. The longan peel extract acted as a strong reducing and stabilizing agent during the synthesis. Water-soluble AgNPs of size 9-32 nm was gathered with a face-centered cubic structure. The AgNPs had potent bactericidal activities against gram-positive and gram-negative bacteria with a dose-related effect. AgNPs also showed dose-dependent cytotoxicity against PC-3 cells through a decrease of stat 3, bcl-2, and survivin, as well as an increase in caspase-3. These findings confirm the bactericidal properties and explored a potential anticancer application of AgNPs for prostate cancer therapy. Further research should be focused on the comprehensive study of molecular mechanism and in vivo effects on the prostate cancer.

Effects of green-synthesized silver nanoparticles on lung cancer cells in vitro and grown as xenograft tumors in vivo.

Silver nanoparticles (AgNPs) have now been recognized as promising therapeutic molecules and are extending their use in cancer diagnosis and therapy. This study demonstrates for the first time the antitumor activity of green-synthesized AgNPs against lung cancer in vitro and in vivo. Cytotoxicity effect was explored on human lung cancer H1299 cells in vitro by MTT and trypan blue assays. Apoptosis was measured by morphological assessment, and nuclear factor-κB (NF-κB) transcriptional activity was determined by a luciferase reporter gene assay. The expressions of phosphorylated stat3, bcl-2, survivin, and caspase-3 were examined by Western blot analysis. AgNPs showed dose-dependent cytotoxicity and stimulation of apoptosis in H1299 cells. The effects on H1299 cells correlated well with the inhibition of NF-κB activity, a decrease in bcl-2, and an increase in caspase-3 and survivin expression. AgNPs significantly suppressed the H1299 tumor growth in a xenograft severe combined immunodeficient (SCID) mouse model. The results demonstrate the anticancer activities of AgNPs, suggesting that they may act as potential beneficial molecules in lung cancer chemoprevention and chemotherapy, especially for early-stage intervention.