Survival Rate Of Cancer Cells Research Articles

Aspirin enhances radio/chemo-therapy sensitivity in C. elegans by inducing germ cell apoptosis and suppresses RAS overactivated tumorigenesis via mtROS-mediated DNA damage and MAPK pathway

Previous studies have demonstrated that combination therapy involving radiotherapy and aspirin decreases the survival rate of cancer cells. However, the mechanism by which aspirin exerts its radiation sensitization effect at the in vivo level remains largely unclear. In this study, we employed Caenorhabditis elegans (C. elegans) as a model organism to investigate the effect of aspirin combined with radio/chemo-therapy on tumors at the individual level. Here, we illustrate that high-dose aspirin increases the expression of genes involved in core apoptosis pathways (egl-1, ced-9, ced-4 and ced-3) and induces germ cell apoptosis in C. elegans through mitochondrial outer membrane permeabilization (MOMP) and elevation of reactive oxygen species (ROS) levels. Crucially, aspirin-induces ROS upregulates the expression of genes critical for DNA damage response (hus-1, clk-2 and cep-1) and genes involved in MAPK pathways (lin-45, mek-2, mpk-1, sek-1 and pmk-1), thereby mediating the enhanced sensitivity of radio/chemo-therapy by aspirin. Notably, aspirin fails to induce germ cell apoptosis and enhance radio/chemo-therapy in C. elegans lacking the expression of each of those genes. Furthermore, in a C. elegans tumor-like symptom model, aspirin enhances radio/chemo-therapy sensitivity through ROS induction. However, low-dose aspirin can diminish the apoptotic signal of reproductive cells in C. elegans and exert anti-inflammatory effects. Our research results suggest that the tumor-suppressive and radio/chemo-therapy sensitizing effects of aspirin provide robust experimental evidence for improving the clinical efficacy of tumor radio/chemo-therapy and deepening our understanding of aspirin's mechanism of action in cancer.

Bilayer 3D co‐culture platform inducing the differentiation of normal fibroblasts into cancer‐associated fibroblast like cells: New in vitro source to obtain cancer‐associated fibroblasts

AbstractThis study presents a novel in vitro bilayer 3D co‐culture platform designed to obtain cancer‐associated fibroblasts (CAFs)‐like cells. The platform consists of a bilayer hydrogel structure with a collagen/polyethylene glycol (PEG) hydrogel for fibroblasts as the upper layer and an alginate hydrogel for tumor cells as the lower layer. The platform enabled paracrine interactions between fibroblasts and cancer cells, which allowed for selective retrieval of activated fibroblasts through collagenase treatment for further study. Fibroblasts remained viable throughout the culture periods and showed enhanced proliferation when co‐cultured with cancer cells. Morphological changes in the co‐cultured fibroblasts resembling CAFs were observed, especially in the 3D microenvironment. The mRNA expression levels of CAF‐related markers were significantly upregulated in 3D, but not in 2D co‐culture. Proteomic analysis identified upregulated proteins associated with CAFs, further confirming the transformation of normal fibroblasts into CAF within the proposed 3D co‐culture platform. Moreover, co‐culture with CAF induced radio‐ and chemoresistance in pancreatic cancer cells (PANC‐1). Survival rate of cancer cells post‐irradiation and gemcitabine resistance increased significantly in the co‐culture setting, highlighting the role of CAFs in promoting cancer cell survival and therapeutic resistance. These findings would contribute to understanding molecular and phenotypic changes associated with CAF activation and provide insights into potential therapeutic strategies targeting the tumor microenvironment.

Polyacrylic acid/polyvinylpyrrolidone/iron oxide nanocarrier for efficient delivery of doxorubicin

Recently, stimuli-responsive drug delivery systems (DDS), especially pH-responsive ones, have drawn a lot of attention to overcome the unfavourable side effects of traditional cancer treatments. In this work, a nanocomposite hydrogel based on polyacrylic acid (PAA), polyvinylpyrrolidone (PVP), and iron oxide (hematite, Fe2O3) nanoparticles was developed using the water/oil/water emulsification technique for the efficient delivery of doxorubicin (DOX) drug. The synthesized nanocarrier was characterized via XRD, and FT-IR to get information about its crystalline structure and the interaction between the functional groups of the different constituents, respectively. Its size distribution and colloidal stability were investigated via DLS and zeta potential tests, and morphological study was carried out by FE-SEM. The nanoparticles were found to be uniform and monodisperse, with an average size of 319 nm and a surface charge of −30.4 mV. The incorporation of hematite increased the drug loading (48.5 %) and encapsulation efficiency (86.57 %) due to its high porosity and surface area. Drug release was tested at pH 7.4 and 5.4, corresponding to healthy and cancerous tissues, and the results demonstrated the pH responsiveness of the system, with faster release (54 % in 24 h) in the acid medium. MTT and flow cytometry tests corroborated its strong anticancer effect since the nano-platform significantly reduced the survival rate of cancer cells. The designed pH-responsive platform holds great potential for breast cancer therapy.

Purification, structural elucidation and in vitro antitumor activity of a novel polysaccharide from sugarcane leaves

Sugarcane leaves have been extensively consumed as a herbal tea for centuries in China, which is an economically important crop containing multiple health benefits. Here we report the structure and in vitro antitumor activity of a purified sugarcane leaf polysaccharide (SLP70–1). SLP70–1 is a homogeneous heteropolysaccharide made up of mannose, glucose, and galactose with a molar ratio of 1.00: 1.89: 2.83. Additionally, the molecular weight of SLP70–1 was 3.23 kDa. Linkage together with NMR examination demonstrated the structural foundation of SLP70–1 were consisted of →4)-α-D-Galp-(1→, →4)-α-D-Glcp-(1→, →2)-β-D-Manp-(1→, →3)-β-D-Galp-(1→, →4,6)-β-D-Galp-(1→, →6)-α-D-Galp-(1→, →3,6)-α-D-Glcp-(1→ and α-D-Glcp-(1→，and the side chain was confirmed to be →4)-α-D-Glcp-(1→ and →6)-α-D-Galp-(1→. According to an in vitro cell experiment, SLP70–1 could markedly decrease the survival ability of cancer cells exhibiting concentration dependence, including the survival rate of cancer cells in the lungs, colon, cervix, kidney, and breast, implying potent antitumor activity. In summary, SLP70–1 exhibits features that qualify it as a promising antitumor adjuvant candidate.

Evaluation of antioxidant properties and cytotoxicity of brown algae (nizamuddinia zanardinii) in uterine (hela) and pancreatic cancer cell lines (paca-2).

Pancreatic cancer and cervical cancer are among the most common cancers. Brown algae have anti-inflammatory, anti-cancer, anti-fungal, antioxidant, and immune-boosting properties. This study investigated the antioxidant properties and the effect of brown algae extract on pancreatic and uterine cancer cells. In this study, Cervical (Hela) and pancreas (Paca-2) cancer cell lines were examined. The algae materials were extracted by sequential maceration method and amount of fucoxanthin content in the sample was determined by using High Performance Liquid Chromatography (HPLC) system. The cytotoxic effect of different concentrations of brown algae was measured by the MTT assay. All statistical calculations for comparing IC50 were analyzed using Graph Pad Prism software. the algal sample contained an average of 102.52 ± 0.12μg of fucoxanthin per 100g. IC50 for 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide free radical scavenging activity for methanolic extract was 2.02 and 11.98 ± 0.13 respectively. Brown algae in all fractions inhibited cell growth and survival. In Hela cell lines, the methanolic extract was the most effective inhibitor, while in Paca cell lines, hexane and methanolic extracts were particularly potent. The methanolic extract was more toxic than other fractions on Hela and Paca cell lines. This study highlights brown algae extracts strong anticancer effects on uterine and pancreatic cancer cells, suggesting its potential as a natural anticancer drug. Different fractions of the extract showed superior apoptotic and cytotoxic effects, with higher concentrations leading to increased apoptotic effects and reduced survival rates of cancer cells.

Nrf2 in human cancers: biological significance and therapeutic potential.

The nuclear factor-erythroid 2-related factor 2 (Nrf2) is able to control the redox balance in the cells responding to oxidative damage and other stress signals. The Nrf2 upregulation can elevate the levels of antioxidant enzymes to support against damage and death. In spite of protective function of Nrf2 in the physiological conditions, the stimulation of Nrf2 in the cancer has been in favour of tumorigenesis. Since the dysregulation of molecular pathways and mutations/deletions are common in tumors, Nrf2 can be a promising therapeutic target. The Nrf2 overexpression can prevent cell death in tumor and by increasing the survival rate of cancer cells, ensures the carcinogenesis. Moreover, the induction of Nrf2 can promote the invasion and metastasis of tumor cells. The Nrf2 upregulation stimulates EMT to increase cancer metastasis. Furthermore, regarding the protective function of Nrf2, its stimulation triggers chemoresistance. The natural products can regulate Nrf2 in the cancer therapy and reverse drug resistance. Moreover, nanostructures can specifically target Nrf2 signaling in cancer therapy. The current review discusses the potential function of Nrf2 in the proliferation, metastasis and drug resistance. Then, the capacity of natural products and nanostructures for suppressing Nrf2-mediated cancer progression is discussed.

Tumor Microenvironment-Responsive 6-Mercaptopurine-Releasing Injectable Hydrogel for Colon Cancer Treatment

Colon cancer is a significant health concern. The development of effective drug delivery systems is critical for improving treatment outcomes. In this study, we developed a drug delivery system for colon cancer treatment by embedding 6-mercaptopurine (6-MP), an anticancer drug, in a thiolated gelatin/polyethylene glycol diacrylate hydrogel (6MP-GPGel). The 6MP-GPGel continuously released 6-MP, the anticancer drug. The release rate of 6-MP was further accelerated in an acidic or glutathione environment that mimicked a tumor microenvironment. In addition, when pure 6-MP was used for treatment, cancer cells proliferated again from day 5, whereas a continuous supply of 6-MP from the 6MP-GPGel continuously suppressed the survival rate of cancer cells. In conclusion, our study demonstrates that embedding 6-MP in a hydrogel formulation can improve the efficacy of colon cancer treatment and may serve as a promising minimally invasive and localized drug delivery system for future development.

The Effect of Berberine Follow by Blue Light Irradiation and Valproic Acid on the Growth Inhibition of MDA-MB-231 Breast Cancer Cells.

Breast cancer is the second most common cancer after lung cancer in the world. Due to the anti-cancer properties of Berberine (Ber), in this study, the effect of combination therapy of Ber in the presence of blue LED irradiation and Valproic acid (Val) on the MDA-MB-231 breast cancer cell line was investigated. For this reason, after culturing the cells using different concentrations of Ber and Val, breast cancer cells were treated in both mono-treatment and combination therapy. In combination therapy, two modes were considered: (1) treatment with Val and then treatment with Ber in the dark or in presence of blue light irradiation (PDT)at a wavelength of 465nm and energy of 30J/cm2 for 15min, and (2) treatment with Ber in the dark or PDT and then treated with Val. In all cases, cell viability, morphological changes, and colonization were assessed. Evaluation of apoptosis was performed by fluorescence microscope and flow cytometry. According to the results, combination therapy has a higher mortality rate compared to mono-treatment, and in combination therapy, treatment of cells first with Ber (10µg/mL)-PDT and then treatment with Val (250µg/mL) caused a significant reduction (P < 0/05) in the survival rate of cancer cells. According to the findings, it can be said that the use of Ber-PDT in combination with Val, in addition to reducing the dose of the drug, has shown a synergistic effect which can suggest the potential of this strategy as a new treatment.

Investigation of antibacterial and anticancer effects of novel niosomal formulated Persian Gulf Sea cucumber extracts

Pharmaceutical companies worldwide are scrambling to develop new ways to combat cancer and microbiological pathogens. The goal of this research was to investigate the antibacterial, anticancer, and apoptosis effects of novel niosomal formulated Persian Gulf Sea cucumber extracts (SCEs). Sea cucumber methanolic extracts were prepared and encapsulated in niosome nanoparticles using thin-film hydration. The compound was made up of Span 60 and Tween 60 blended with cholesterol in a 3:3:4 M ratios. Characterization of niosome-encapsulated SCE evaluated by scanning electron microscopy and transmission electron microscopy. The disk diffusion method and microtiter plates were used to investigate the antimicrobial activity. The effect of niosome-encapsulated SCE on cell proliferation and apoptosis induction was studied using MTT and Annexin V, respectively. The expression of apoptosis-related genes, including Bax, Fas, Bax, Bak, and Bcl2, was studied using quantitative real-time PCR. Niosome-encapsulated SCE with a size of 80.46 ± 1.31 and an encapsulation efficiency of 79.18 ± 0.23 was formulated. At a concentration of 100 μg/ml, the greatest antimicrobial effect of the niosome-encapsulated SCE was correlated to Staphylococcus aureus, with an inhibition zone of 13.16 mm. The findings of the study revealed that all strains were unable to produce biofilms at a concentration of 100 μg/ml niosome-encapsulated SCE (p < 0.001). The survival rate of cancer cells after 72 h of exposure to niosome-encapsulated SCE was 40 ± 3.0%. Encapsulated SCE in niosomes inhibited cell progression in MCF-7 cells by increasing G0/G1 and decreasing S phase relative to G2/M phase; as a result, it activated the apoptosis signaling pathway and led to the induction of apoptosis in 69.12 ± 1.2% of tumor cells by increasing the expression of proapoptotic genes (p < 0.001). The results indicate that sea cucumber species from the Persian Gulf are a promising source of natural chemicals with antibacterial and anticancer properties, paving the path for novel marine natural products to be discovered. This is the first demonstration that niosome-encapsulated SCE contains antibacterial and anticancer chemicals that, according to their specific characteristics, boost antitumor activity.

Ag2–3xBixS Quantum Dots as Single-Component Theranostic Agents for Second Near-Infrared Fluorescence Imaging-Guided Photothermal Therapy

Silver sulfide (Ag2S) nanomaterials are being researched increasingly because of their multifunctional potential in the second near-infrared (NIR-II) region (1000–1500 nm). Here, we report Ag2–3xBixS quantum dots (Ag2–3xBixS QDs) as single-component theranostic nanomaterials for NIR-II fluorescence imaging and synchronous photothermal therapy. Bismuth doping in Ag2S QDs leads to a fluorescence red shift to the NIR-II region and simultaneously enhances the photothermal conversion efficiency to 58.9%, which can be ascribed to the altered band gap introduced by bismuth doping. This Ag2S-based NIR-II theranostic agent can be synthesized in a controlled manner by an albumin biomineralization method under mild conditions. The encapsulation of the biomacromolecular albumin endowed Ag2–3xBixS QDs with greatly strengthened biocompatibility and stability. The survival rate of cancer cells was only 13% after irradiation with an 808 nm laser at a density of 1.2 W cm–2 for 10 min. Meanwhile, in vivo experiments have confirmed the desirable NIR-II fluorescence imaging capability of Ag2–3xBixS QDs. Thus, this study provides a highly efficient single-component theranostic agent with great promise for application in the field of precision theranostics.

Monitoring and Regulating Intracellular GPX4 mRNA Using Gold Nanoflare Probes and Enhancing Erastin-Induced Ferroptosis.

Glutathione peroxidase 4 (GPX4) plays an important effect on ferroptosis. Down-regulating the expression of GPX4 mRNA can decrease the content of GPX4. In this work, a gold nanoflare (AuNF) probe loaded with anti-sense sequences targeting for GPX4 mRNA was designed to monitor and down-regulate intracellular GPX4 mRNA using fluorescence imaging in situ and using anti-sense technology. The results revealed that there was a marked difference for the expression of GPX4 mRNA in different cell lines, and the survival rate of cancer cells was not significantly effected when the relative mRNA and protein expression levels of GPX4 was down-regulated by AuNF probes. However, when co-treated with AuNF probes, the low expression of GPX4 strengthened erastin-induced ferroptosis, and this synergy showed a better effect on inhibiting the proliferation of cancer cells.

Evaluation of the Cytotoxic Effects of Concomitant Use of Ag/ZnO Nanoparticles and Curcumin on MCF7 Breast Cancer Cell Line

Introduction: Cancer is the second cause of death. The use of a new drug delivery system that can deliver the drug to the tumor site and prevent it from entering the body's natural tissues is essential. Metal oxide nanoparticles have been considered one of the effective candidates for cancer treatment. For this reason, our study was conducted to investigate the cytotoxic effect of the simultaneous use of Ag/ZnO nanoparticles and curcumin on the Michigan Cancer Foundation-7 (MCF7) breast cancer cell line. Method: The MTT colorimetric method was used to investigate the synergistic effects of zinc oxide silver nanoparticles and curcumin. Cells with different concentrations of zinc oxide silver nanoparticles and curcumin, including 3.9, 7.8, 15.62, 31.25, 62.5, 125, 250, 500, and 1000 micrograms/ml during 24 and 48 h were incubated in triplicate to observe the synergistic effects of each of these concentrations, ratios of 1 to 1, 0.5 to 0.5, 0.25 to 0.75 of zinc oxide silver nanoparticles and curcumin were used. The viability of the cells treated with the drug was determined in the form of the percentage of light absorption of the produced formazan and was shown in a two-dimensional curve. Results: The effect of Ag/ZnO nanoparticles alone on the survival rate of cancer cells had a significant difference with curcumin. In addition, in the simultaneous examination of Ag/ZnO nanoparticles and curcumin, much more cytotoxicity was observed than in Ag/ZnO alone. Conclusion: In general, the simultaneous use of chemotherapy drugs and nanoparticles can decrease the concentration of chemotherapy drugs used in cancer treatment.

In vitro and Pharmacoinformatics-based phytochemical screening for anticancer impacts of pistachio hull essential oil on AGS, PLC/PRF/5, and CACO2 cell lines.

The essential oil of pistacia vera (cv. Ohadi) hull (PHEO) was checked using gas chromatography mass spectrometry (GC/MS) analysis. It was studied the genes of the wnt pathway with a certain concentration of PHEO on Human gastric cancer (AGS), human hepatocellular carcinoma (PLC/PRF/5), and human colon cancer (CACO2) cell lines. After evaluating the survival rate of cancer cells by MTT test and determining IC50, pistachio hull essential oil (PHEO) was used for 24-hours to treat the cells. After RNA extraction, the expression of wnt pathway genes was evaluated by Real-Time PCR. Considering the crucial role of β-catenin accumulation and its effect on the progression of gastrointestinal cancers, Western blot analysis was also used to determine the effect of PHEO in protein expression of β-catenin inhibition. Also, an in silico analysis was carried out to investigate the effect of PHEO extracted compounds on protein expression of β-catenin and FZD7 inhibition. According to the results, wnt pathway genes were changed in samples treated using PHEO. The results showed the up-regulation of GSK-3β and down-regulation of Wnt-1, LEF-1, TCF1, and CTNNB1 genes compared to the control. We showed inhibition of β-catenin protein in cancer cell lines. Four compounds of PHEO were suggested to have an inhibition effect on β-catenin and FZD7. These compounds can be useful in the treatment of gastrointestinal cancers. Altogether, the inhibitory role of β-catenin protein can be very effective and can be considered one of the therapeutic goals in the treatment of gastrointestinal cancers.

Study on the photothermal performance of supra-(carbon nanodots) developed with dicyandiamide N-doped

In the present work, the dicyandiamide N-doped supra-CNDs were synthesized just within 24 h. The supra-CNDs exhibited a new strong absorption band at longer wavelengths (450–900 nm) and higher photothermal conversion efficiency (55.49 % and 46.02 % irradiation at 730 nm and 808 nm, respectively). The supra-CNDs can still maintain excellent photothermal stability and reusability after three on/off cycles. The survival rate of cancer cells incubated with supra-CNDs was above 90 %, but the value was drastically reduced to 4.24 % and 7.25 % after strong photothermal ablation at 730 nm and 808 nm, respectively. The cell killing ability of the supra-CNDs was also validated by photothermal ablation experiment. The excellent photothermal performance and low toxicity make the supra-CNDs highly promising application in photothermal therapy.

Effect of Rosemary Essential Oil on BIM Apoptotic Gene Expression in MCF 7 Breast Cancer Cell Line

Introduction: Breast cancer is the most common cancer among women and its treatment is associated with many side effects. Herbal medicine has fewer side effects than chemical drugs, so they are especially important in the treatment of many diseases. Rosemary plant has anti-cancer effects due to its antioxidant properties. The aim of this study was to evaluate the effect of Rosemary essential oil on BIM gene expression in MCF-7 cell line.&#x0D; Methods: In this experimental study, to evaluate the cellular toxicity of rosemary essential oil, MCF-7 cells were exposed to different concentrations of essential oil for 24, 48 and 72 hours, and their survival was investigated using MTT assay. Then, MCF-7 cells were exposed to essential oil for 24 hours to determine the BIM gene expression using the Real Time PCR technique. Statistical analysis of data was performed using T-Student test and SPSS version 16 software.&#x0D; Results: The results of the MTT assay show that cell death is dose- and time-dependent. The effect of different amounts of essential oil on the survival rate of cancer cells was statistically significant (p˂0.05) and the lowest survival rate was 19% in 72 hours and with increasing essential oil concentration, cell death also increased. Real Time PCR results show a significant increase in BIM gene expression after essential oil treatment.&#x0D; Conclusion: In conclusion, the results of this study demonstrate the cytotoxic effect of rosemary essential oil on breast cancer cells and it can increase the expression of BIM, an apoptotic gene and induce anticancer effects.

Toxicity Effects of Lipid Nanoparticles Containing Artemisia Absinthium L Essential Oil on BRC-03 Breast Cancer Cell Line

Background &amp; Objective: According to research, breast cancer is the second most common cancer among women. Nanomaterials of various materials significantly increase the solubility, stability and effective drug delivery, and in recent years research on the effectiveness of essential oils and plant extracts in inhibiting the growth of cancer cells is expanding. Artemisia belongs to the Asteraceae family. In many studies, the effectiveness of the essential oil and extract of this plant in inhibiting the growth of cancer cells has been reported.&#x0D; Materials &amp; Methods: In this experiment, nanoparticles containing Artemisia absinthium L essential oil (thistle) were first synthesized by homogenizer &amp; sonication method and then their physicochemical properties were determined, such as particle size, particle size distribution, zeta potential, percentage of loading efficiency. Then, the anti-apoptotic effect of lipid nanoparticles containing Artemisia essential oil in breast cancer cells (BRC-03) was evaluated.&#x0D; Results: The results of cellular effect of lipid nanoparticles containing essential oil of Artemisia absinthium L (thistle) on breast cancer cells showed that increasing the concentration of lipid nanoparticles containing essential oil of this plant reduced the survival rate of cancer cells. Breast (BRC-03) was purified compared to essential oil (p &lt;0.05).&#x0D; Conclusion: Nano-essential oil of this plant is effective in reducing the IC50 of the drug and in increasing the cytotoxicity of the essential oil of the plant. Lipid nanoparticles containing essential oil of Artemisia absinthium L (thistle) activated the apoptotic pathway in breast cancer cells.

Anchoring Pd nanoparticles on hollow CuS nanoparticles for enhanced NIR induced photothermal effects for chemotherapeutic drug delivery and gastric cancer treatment

Traditional cancer chemotherapy has resulted in nonspecific drug delivery, low cellular anticancer drug uptake, and severe side effects to normal tissues. Near-infrared (NIR)-responsive photothermal therapy has emerged as a new non-invasive cancer treatment with more controllable drug delivery, higher anticancer efficacy, and reduced side effects. Noble metal nanomaterials possess superior photothermal and optical properties, but the high cost and scarcity limit their applications in biomedical fields. Herein, we reported the synthesis of Pd nanoparticles anchored hollow CuS nanospheres (CuS/Pd composite) as drug carriers for NIR-induced drug delivery and cancer treatment. The CuS/Pd composite shows significantly enhanced photothermal properties in comparison with CuS. The cytotoxicity test indicates the high biocompatibility of CuS/Pd. Notably, the NIR-triggered effective and controllable release of loaded doxorubicin (DOX) under NIR laser irradiation is successfully demonstrated. A series of cell viability experiments show that the survival rate of cancer cells with CuS/Pd/TD/DOX is as low as ∼20%. In addition, the CuS/Pd composite exhibits excellent material stability. Therefore, this work sheds light on the design and synthesis of low-cost and effective drug carriers for enhanced NIR-induced drug delivery and cancer treatment.

Combination of chemotherapy and photothermal methods for in vitro ablation of MCF-7 cancer cells using crinkly core–shell structure MoS2/C@SiO2 nanospheres

MoS2/C@SiO2 spheres were successfully synthesized by a one-step hydrothermal method using silica as the template, sodium molybdate as the Mo source and glucose as the carbon precursor. In this paper, the antitumor ability of MoS2/C@SiO2 and C@SiO2 nanospheres was evaluated through the photothermal effect induced by near infrared (NIR) spectroscopy and the drug loading and release behaviors of the model drug doxorubicin (DOX). The photothermal conversion efficiency (η) of MoS2/C@SiO2 of 42.5% was 1.2 times that of C@SiO2 (34.7%), which indicated its significant photothermal effect. The drug loading of MoS2/C@SiO2 of 46.5% was much higher than that of C@SiO2 (12.4%); it was 3.75 times that of C@SiO2. The cumulative drug release of MoS2/C@SiO2 and C@SiO2 under a simulated acidic tumor environment and NIR irradiation was 58.9% and 27.29%, respectively. Moreover, the cell viability assays verified that MoS2/C@SiO2-DOX had excellent antitumor ability under the co-stimulation of endogenous (pH) and exogenous (NIR) compared with C@SiO2-DOX. The experimental results showed that the survival rate of cancer cells in MoS2/C@SiO2-DOX under coordinated treatment was only 19.4%, while that of C@SiO2-DOX was 24.6%.

Circ-METTL15 contributes to the proliferation, metastasis, immune escape and restrains apoptosis in lung cancer by regulating miR-1299/PDL1 axis

Background Circular RNAs (circRNAs) are important regulators in the pathogenesis of lung cancer. The study aims to explore the function and mechanism of circRNA methyltransferase-like 15 (circ-METTL15) in lung cancer development. Methods The expression of circ-METTL15, miR-1299 and programmed death-ligand 1 (PDL1) were investigated by qRT-PCR assay. Cell viability, colony formation, cell proliferation and invasion were determined by MTT, colony formation, EDU incorporation and transwell assays, respectively. Cell apoptosis was attested by flow cytometry and TUNEL assays. Interferon-γ (IFN-γ) and Tumour Necrosis Factor-α (TNF-α) production were tested by enzyme-linked immunosorbent assay (ELISA), and the survival rate of cancer cells was assessed by cytotoxicity analysis. The protein expression was examined by western blot or immunohistochemistry (IHC) assay. The interaction between miR-1299 and circ-METTL15 or PDL1 was confirmed via dual-luciferase reporter assay. Xenograft models were established in mice to explore the role of circ-METTL15 in tumour growth in vivo. Results Circ-METTL15 was upregulated in lung cancer tissues and cells. Circ-METTL15 silencing suppressed cell proliferation, colony formation, invasion, immune escape and promoted cell apoptosis in lung cancer cells. Circ-METTL15 was a sponge of miR-1299, and it could exert regulatory function in lung cancer via miR-1299. Furthermore, PDL1 was a functional target of miR-1299, and miR-1299 inhibited lung cancer cell development via decreasing PDL1 expression. Moreover, circ-METTL15 controlled PDL1 expression by acting as a sponge of miR-1299. Besides, circ-METTL15 downregulation blocked lung cancer tumour growth in vivo by regulating the miR-1299/PDL1 axis. Conclusion Circ-METTL15 promoted lung cancer malignant progression at least partly through modulating PDL1 by sponging miR-1299.

Inhibition of SREBP-mediated lipid biosynthesis and activation of multiple anticancer mechanisms by platinum complexes: Ascribe possibilities of new antitumor strategies

Cancer is one of the most aggressive diseases with poor prognosis and survival rates. Lipids biogenesis play key role in cancer progression, metastasis and tumor development. Suppression of SREBP-mediated lipid biogenesis pathway has been linked with cancer inhibition. Platinum complexes bearing good anticancer effect and multiple genes activation properties are considered important and increase the chances for development of new platinum-based drugs. In this study, we synthesized pyridine co-ligand functionalized cationic complexes and characterized them using multiple spectroscopic and spectrophotometric methods. Two of these complexes were studied in solid state by single crystal X-ray analysis. The stability of these complexes were measured in solution state using 1H NMR methods. These complexes were further investigated for their anticancer activity against human breast, lung and liver cancer cells. MTT assay showed potential cytotoxic activity in dose-dependent manner and decrease survival rates of cancer cells was observed upon treatment with these complexes. Biological assays results revealed higher cytotoxicity as compared to cisplatin and oxaliplatin. Further we studied C2, C6 and C8 in detailed mechanistic anticancer analyses. Clonogenic assay showed decrease survival of MCF-7, HepG2 and A549 cancer cells treated with C2, C6 and C8 as compared to control cells treated with DMSO. TUNEL assay showed more cell death, these complexes suppressed invasion and migration ability of cancer cells and decreased tumor spheroids formation, thus suggesting a potential role in inhibition of cancer metastasis and cancer stem cells formation. Mechanistically, these complexes inhibited sterol regulatory element-binding protein 1 (SREBP-1) expression in cancer cells in dose-dependent manner and thereby reduced lipid biogenesis to suppress cancer progression. Furthermore, expression level was decreased for the key genes LDLR, FASN and HMGCR, those required for sterol biosynthesis. Taken together, these complexes suppressed cancer cell growth, migration, invasion and spheroids formation by inhibiting SREBP-1 mediated lipid biogenesis pathway.