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4.
Int J Mol Med ; 47(3): 1, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33448317

RESUMEN

Coronavirus disease 2019 (COVID­19), caused by severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2), was identified in December, 2019 in Wuhan, China. Since then, it has continued to spread rapidly in numerous countries, while the search for effective therapeutic options persists. Coronaviruses, including SARS­CoV­2, are known to suppress and evade the antiviral responses of the host organism mediated by interferon (IFN), a family of cytokines that plays an important role in antiviral defenses associated with innate immunity, and has been used therapeutically for chronic viral diseases and cancer. On the other hand, OncoTherad, a safe and effective immunotherapeutic agent in the treatment of non­muscle invasive bladder cancer (NMIBC), increases IFN signaling and has been shown to be a promising therapeutic approach for COVID­19 in a case report that described the rapid recovery of a 78­year­old patient with NMIBC with comorbidities. The present review discusses the possible synergistic action of OncoTherad with vitamin D, zinc and glutamine, nutrients that have been shown to facilitate immune responses mediated by IFN signaling, as well as the potential of this combination as a therapeutic option for COVID­19.


Asunto(s)
Antivirales/farmacología , Glutamina/farmacología , Glicoproteínas/farmacología , Factores Inmunológicos/uso terapéutico , Interferones/metabolismo , Fosfatos/farmacología , Vitamina D/farmacología , Zinc/farmacología , Anciano , Antivirales/uso terapéutico , Comorbilidad , Sinergismo Farmacológico , Glicoproteínas/uso terapéutico , Humanos , Inmunidad Innata/efectos de los fármacos , Factores Inmunológicos/farmacología , Masculino , Fosfatos/uso terapéutico , Cálculos de la Vejiga Urinaria/tratamiento farmacológico , Cálculos de la Vejiga Urinaria/epidemiología
11.
Nat Commun ; 12(1): 440, 2021 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-33469052

RESUMEN

The main challenges for programmed cell death 1(PD-1)/PD-1 ligand (PD-L1) checkpoint blockade lie in a lack of sufficient T cell infiltration, tumor immunosuppressive microenvironment, and the inadequate tumor accumulation and penetration of anti-PD-1/PD-L1 antibody. Resetting tumor-associated macrophages (TAMs) is a promising strategy to enhance T-cell antitumor immunity and ameliorate tumor immunosuppression. Here, mannose-modified macrophage-derived microparticles (Man-MPs) loading metformin (Met@Man-MPs) are developed to efficiently target to M2-like TAMs to repolarize into M1-like phenotype. Met@Man-MPs-reset TAMs remodel the tumor immune microenvironment by increasing the recruitment of CD8+ T cells into tumor tissues and decreasing immunosuppressive infiltration of myeloid-derived suppressor cells and regulatory T cells. More importantly, the collagen-degrading capacity of Man-MPs contributes to the infiltration of CD8+ T cells into tumor interiors and enhances tumor accumulation and penetration of anti-PD-1 antibody. These unique features of Met@Man-MPs contribute to boost anti-PD-1 antibody therapy, improving anticancer efficacy and long-term memory immunity after combination treatment. Our results support Met@Man-MPs as a potential drug to improve tumor resistance to anti-PD-1 therapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Micropartículas Derivadas de Células/inmunología , Portadores de Fármacos/farmacología , Neoplasias/tratamiento farmacológico , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Línea Celular Tumoral , Sinergismo Farmacológico , Femenino , Humanos , /uso terapéutico , Memoria Inmunológica , Masculino , Metformina/farmacología , Metformina/uso terapéutico , Ratones , Neoplasias/inmunología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Células RAW 264.7 , Escape del Tumor/efectos de los fármacos , Escape del Tumor/inmunología , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , /inmunología , Ensayos Antitumor por Modelo de Xenoinjerto
12.
Molecules ; 26(2)2021 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-33477259

RESUMEN

Over the past 20-30 years, Trichophyton rubrum represented the most widespread dermatophyte with a prevalence accounting for 70% of dermatophytosis. The treatment for cutaneous infections caused by Trichophyton spp. are imidazoles (ketoconazole (KTZ)) and triazoles (itraconazole (ITZ)). T. rubrum can develop resistance to azoles after prolonged exposure to subinhibitory concentrations resulting in therapeutic failures and chronic infections. These problems have stimulated the search for therapeutic alternatives, including essential oils, and their potential use in combination with conventional antifungals. The purpose of this study was to evaluate the antifungal activity of tea tree oil (TTO) (Melaleuca alternifolia essential oil) and the main components against T. rubrum and to assess whether TTO in association with KTZ/ITZ as reference drugs improves the antifungal activity of these drugs. We used a terpinen-4-ol chemotype (35.88%) TTO, and its antifungal properties were evaluated by minimum inhibitory and minimum fungicidal concentrations in accordance with the CLSI guidelines. The interaction between TTO and azoles was evaluated through the checkerboard and isobologram methods. The results demonstrated both the fungicide activity of TTO on T. rubrum and the synergism when it was used in combination with azoles. Therefore, this mixture may reduce the minimum effective dose of azole required and minimize the side effects of the therapy. Synergy activity offered a promise for combination topical treatment for superficial mycoses.


Asunto(s)
Antifúngicos , Arthrodermataceae/crecimiento & desarrollo , Itraconazol , Cetoconazol , Melaleuca/química , Aceite de Árbol de Té , Antifúngicos/química , Antifúngicos/farmacología , Sinergismo Farmacológico , Itraconazol/agonistas , Itraconazol/química , Itraconazol/farmacología , Cetoconazol/agonistas , Cetoconazol/química , Cetoconazol/farmacología , Aceite de Árbol de Té/química , Aceite de Árbol de Té/farmacología
13.
J Cancer Res Clin Oncol ; 147(3): 691-701, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33389078

RESUMEN

BACKGROUND: Some chemotherapy drugs have immunomodulatory effects on specific tumors. The potential of vincristine (VCR) in the R-CHOP regimen to act as both a chemotherapeutic and an immunomodulatory agent via PD-L1 in tumor cells remains unclear. METHODS: In vitro screening VCR showed that the IC50 value of VCR in the DLBCL cell lines was approximately 2 nM. Western blotting and q-PCR were used to detect the expression of PD-L1. The effect of VCR combined with PD-L1 mAb was tested in a co-culture system of LY-OCI-3 cells and peripheral blood mononuclear cells and in DLBCL xenograft mouse model. Flow cytometry was used to determine the proportion of T lymphocyte subsets. The effect of the STAT3 inhibitor nifuroxazide on VCR-induced PD-L1 expression was tested in LY-OCI-3 and SU-DHL-4 cells. RESULTS: VCR upregulated PD-L1 protein and mRNA expression in various DLBCL cell lines. PD-L1 Ab combined with VCR significantly increased the proportion of CD8 + Granzyme B + , INF-γ + or TNF-α + CD3 + T cells. VCR + PD-L1 Ab inhibited tumor growth more effectively than VCR monotherapy, whereas PD-L1 Ab alone had no significant effect. Survival time did not differ significantly between the PD-L1 Ab group and the control group, whereas it was significantly longer in the VCR monotherapy and combination groups which showed more longer survival compared with the former. Nifuroxazide downregulated p-STAT3 and PD-L1 protein levels. CONCLUSIONS: VCR upregulated PD-L1 expression in DLBCL cells partially by promoting the p-STAT3; VCR combined with PD-L1 Ab activated effector T cells and increased the antitumor immune response in vitro and in vivo.


Asunto(s)
Antineoplásicos Inmunológicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Antígeno B7-H1/biosíntesis , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Vincristina/farmacología , Animales , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/inmunología , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Línea Celular Tumoral , Sinergismo Farmacológico , Femenino , Humanos , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Distribución Aleatoria , Regulación hacia Arriba/efectos de los fármacos , Vincristina/administración & dosificación , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Int J Mol Sci ; 22(2)2021 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-33466734

RESUMEN

Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes. The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson's disease, Tourette's syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been proven so far, results from the affinity of these compounds predominantly for the receptors of the endocannabinoid system (the cannabinoid receptor type 1 (CB1), type two (CB2), and the G protein-coupled receptor 55 (GPR55)) but, also, for peroxisome proliferator-activated receptor (PPAR), glycine receptors, serotonin receptors (5-HT), transient receptor potential channels (TRP), and GPR, opioid receptors. The synergism of action of phytochemicals present in Cannabis sp. raw material is also expressed in their increased bioavailability and penetration through the blood-brain barrier. This review provides an overview of phytochemistry and pharmacology of compounds present in Cannabis extracts in the context of the current knowledge about their synergistic actions and the implications of clinical use in the treatment of selected diseases.


Asunto(s)
Cannabinoides/farmacología , Cannabis/química , Descubrimiento de Drogas , Fitoquímicos/farmacología , Terpenos/farmacología , Animales , Cannabinoides/química , Cannabinoides/uso terapéutico , Sinergismo Farmacológico , Endocannabinoides/metabolismo , Epilepsia/tratamiento farmacológico , Epilepsia/metabolismo , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Fitoquímicos/química , Fitoquímicos/uso terapéutico , Receptores de Cannabinoides/metabolismo , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/metabolismo , Terpenos/química , Terpenos/uso terapéutico , Síndrome de Tourette/tratamiento farmacológico , Síndrome de Tourette/metabolismo
15.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(1): 124-128, 2021 Jan.
Artículo en Chino | MEDLINE | ID: mdl-33474901

RESUMEN

Objective: To explore the significance of the resistance to polymyxin resistance of the extensively drug resistant Acinetobacter baumannii (XDRAB) lipopolysaccharide (LPS) lpx A, lpx C, lpx D and to screen appropriate combination therapy. Methods: In the past two years, 72 XDRAB in the secretions of our patients were selected as the research object. According to the minimum inhibitory concentration (MIC) of the XDRAB strain on polymyxin, they were included in the drug resistance group and the sensitive group. The gene sequences of strains lpx A, lpx C, lpx D were compared with the standard strains to analyze gene mutations and compared the mutation rates in the drug resistant group and the sensitive group. The efficacy of the combination drugs was evaluated by microcheckerboard dilution method, including polymyxin+imipenem group, polymyxin+meropenem group, polymyxin+cefoperazone/sulbactam group, polymyxin+levofloxacin group, and polymyxin+fosfomycin group. Calculated the fractional inhibitory concentration (FIC) index of the combined medication regimen and compared the percentage of strains that exhibited synergistic, additive, irrelevant, and antagonistic effects. Results: Tentyone were in the drug resistant group, accounting for 21 (29.17%,) and 51 were in the sensitive group, accounting for 70.83%. Some strains had mutations in lpx A, lpx C, lpx D genes. The mutation rate in the drug resistant group was 90.48%, which was significantly higher than 11.76% in the sensitive group, the difference was statistically significant ( P<0.05). The combined drug sensitivity test showed, compared with the polymyxin+fosfomycin group, the mycotin+fosfomycin group had a higher percentage of strains with synergistic FIC index in the polymyxin+imipenem group, the difference was statistically significant ( P<0.01). Conclusion: XDRAB is resistant to polymyxin, which is related to mutations in LPS lipid A biosynthesis genes lpx A, lpx C, lpx D. Clinical treatment should adopt a combination of polymyxin+imipenem/meropenem and other drug combination to reduce the secondary infection of drug resistant bacteria.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Infecciones por Acinetobacter/tratamiento farmacológico , Acinetobacter baumannii/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Sinergismo Farmacológico , Humanos , Lípido A , Lipopolisacáridos , Pruebas de Sensibilidad Microbiana , Mutación , Polimixinas/farmacología
16.
Int J Nanomedicine ; 16: 269-281, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33469286

RESUMEN

Background: Rapamycin is a promising agent for treating tumors, but clinical applications of rapamycin are limited due to its poor water solubility and low bioavailability. This paper constructs a liposome delivery system for rapamycin to improve the effect in treating colorectal cancer. Methods: We prepared the rapamycin liposomes using the ethanol injection method. The cellular uptake and biodistribution were detected by LC-MS and in vivo imaging system. MTT assay, transwell migration experiment, flow cytometry, and Western blot analysis evaluated the antitumor effect of rapamycin liposomes in vitro. Furthermore, HCT-116 tumor-bearing mice were used to assess the therapeutic efficacy of rapamycin liposomes in vivo. Results: The prepared rapamycin liposomes had a particle size of 100±5.5 nm and with a narrow size distribution. In vitro cellular uptake experiments showed that the uptake of rapamycin liposomes by colorectal cells was higher than that of free rapamycin. Subsequently, in vivo imaging experiments also demonstrated that rapamycin liposomes exhibited higher tumor accumulation. Therefore, the ability of rapamycin liposomes to inhibit tumor proliferation, migration and to induce tumor apoptosis is superior to that of free rapamycin. We also demonstrated in vivo good antitumor efficacy of the rapamycin liposomes in HCT-116 xenograft mice. In addition, rapamycin liposomes and 5-FU can synergistically improve the efficacy of colorectal cancer via the Akt/mTOR and P53 pathways. Conclusion: Collectively, rapamycin liposomes are a potential treatment for colorectal cancer, as it not only improves rapamycin's antitumor effect but also synergistically enhances 5-FU's chemotherapy effect.


Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Sirolimus/administración & dosificación , Sirolimus/uso terapéutico , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/patología , Sinergismo Farmacológico , Fluorouracilo/administración & dosificación , Fluorouracilo/farmacología , Humanos , Concentración 50 Inhibidora , Liposomas , Ratones , Tamaño de la Partícula , Transducción de Señal/efectos de los fármacos , Sirolimus/farmacología , Distribución Tisular , Ensayo de Tumor de Célula Madre , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Ecotoxicol Environ Saf ; 208: 111664, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396174

RESUMEN

Recently, the pollution of microplastics (MPs) in the global freshwater environment has become increasingly problematic, but there are few studies on the freshwater environment risks of MPs. The present study, therefore, has investigated the single and combined effects of MPs and lead (Pb) on the freshwater algal Microcystis aeruginosa. Results showed that Pb-only (>0.05 mg·L-1) promoted the growth of algal cells, while MPs-only (1 mg L-1) resulted in growth inhibition. However, compared with the corresponding concentration of Pb-only groups, the growth of algal cells was promoted in MPs + Pb treatments. MPs-only and Pb-only (0.5 mg L-1) both reduced the content of photosynthetic pigments and affected algal photosynthesis. The MPs-only treatment and MPs + Pb2+ (no pretreatment, 0.5 mg L-1 Pb2+) treatments showed significant cell aggregation. At the same time, MPs-only caused a significant increase in bound extracellular polysaccharides (bEPS), while 0.5 mg L-1 Pb reduced bEPS. Furthermore, under high Pb stress (0.5 mg L-1), the effects of combined MPs and Pb on chlorophyll content, antioxidant enzyme activity (peroxidase (POD), catalase (CAT)), and damage to algal cells were less compared to individual effects, and the combination of MPs and Pb had a synergistic effect on promoting aggregations of M. aeruginosa. These results demonstrate that single and combined effects of MPs and Pb can induce differential responses in the freshwater algal M. aeruginosa, which can have a significant impact on aquatic ecosystems.


Asunto(s)
Agua Dulce/microbiología , Plomo/toxicidad , Microcystis/efectos de los fármacos , Microplásticos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Antioxidantes/metabolismo , Clorofila/metabolismo , Sinergismo Farmacológico , Ecosistema , Agua Dulce/química , Microcystis/crecimiento & desarrollo , Microcystis/metabolismo , Fotosíntesis/efectos de los fármacos
18.
J Ethnopharmacol ; 264: 113388, 2021 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-32918990

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Kanglaite (KLT) is an active extract of the Coix lacryma-jobi seed, which can benefit Qi and nourish Yin, and disperse the accumulation of evils. It is used as a biphasic broad-spectrum anti-cancer drug, and shows synergistic effects with radiotherapy and chemotherapy. However, the mechanism of KLT combined with cisplatin (CDDP) against hepatocellular carcinoma (HCC) has not been elucidated. AIM OF THE STUDY: The aim of present study was to investigate the potential synergistic effects of KLT and CDDP on HepG2 cells, discussing the possible mechanisms from the perspective of CKLF1 and NF-κB mediated inflammatory response and chemoresistance, and the involvement of drug efflux transporters. MATERIALS AND METHODS: CDDP injured HepG2 cells were used to investigate the effects of KLT on chemotherapeutics treated HCC. Effects of KLT pretreatment on CDDP injured HepG2 cells were determined by MTT, wound healing assay, and transwell assay. Expression of chemokine-like factor 1 (CKLF1) and activation of nuclear factor κB (NF-κB) were examined by qPCR, western blot, and immunofluorescence staining. Furthermore, to study the role of CKLF1 in KLT mediated effects on this CDDP injured HCC cell model, HepG2 cells overexpressed with CKLF1 gene were used. Cell viability and NF-κB activation were investigated. Moreover, TNF-α and IL-1ß levels were measured by Elisa analysis and western blot to evaluate the inflammatory response. Additionally, ATP-binding cassette (ABC) drug efflux transporters, MDR1, MRP2, and BCRP were also determined in present study. RESULTS: KLT pretreatment followed by CDDP treatment was found to show synergistic effects, which showed by decreased cell viability, migration and invasion ability of HepG2 cells. Expression of CKLF1 enhanced significantly in CDDP treated HepG2 cells, and KLT decreased this elevation obviously. Furthermore, CDDP activated NF-κΒ and promoted translocation of NF-κB toward the nucleus. KLT inhibited the activation of NF-κΒ, which sensitized cancer cells. Overexpression of CKLF1 reversed the effects of KLT on CDDP injured HepG2 cells, which exhibited by increased cell viability and enhanced activation of NF-κΒ. CDDP induced NF-κΒ activation could also lead to excessive inflammatory response, and KLT can suppress the aggravating inflammation which may be beneficial for tumor progression. Furthermore, we found that ABC drug efflux transporters MDR1, MRP2, and BCRP in CDDP treated HepG2 cells were decreased when pretreated with KLT. CONCLUSIONS: KLT pretreatment may increase the effects of CDDP on HepG2 cells, by exhibiting cooperative effects on suppression of HepG2 cells. The mechanisms may partly by inhibiting CKLF1 mediated NF-κB pathway, which may contribute to inflammation of tumor microenvironment and chemoresistance of CDDP. Inhibition of transporter-mediated drug efflux is also involved in KLT mediated sensitization effects of CDDP.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Quimiocinas/metabolismo , Cisplatino/administración & dosificación , Medicamentos Herbarios Chinos/administración & dosificación , Neoplasias Hepáticas/metabolismo , Proteínas con Dominio MARVEL/metabolismo , FN-kappa B/metabolismo , Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Quimiocinas/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Proteínas con Dominio MARVEL/antagonistas & inhibidores , Proteínas de Transporte de Membrana/metabolismo , FN-kappa B/antagonistas & inhibidores , Resultado del Tratamiento
19.
Food Chem ; 335: 127576, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32739805

RESUMEN

The main causes of food spoilage come from the process of oxidation and the contamination by microorganisms. For the purpose of increasing food shelf-life the industries employ different techniques, being the addition of preservatives, one of the most used. The aim of this contribution was to investigate the potential antioxidant properties of tyrosol (4-hydroxyphenethyl alcohol, 4-OH) and tyrosol derived isomers (2-hydroxyphenethyl alcohol, 2-OH and 3-hydroxyphenethyl alcohol, 3-OH) against reactive oxygen species (ROS) and the antimicrobial effect on Staphylococcus aureus and Escherichia coli. Furthermore, the type of antioxidant effect of substrates and commercial antioxidants mixtures was studied. Upon visible-light, the substrates interacted with the vitamin B2 and different ROS were generated. All the compounds deactivated O2(1Δg) and O2●-, whereas only 2-OH and 3-OH inhibited H2O2 and HO●. The substrates exhibited a synergistic antioxidant effect when combined with commercial antioxidants. 2-OH showed antimicrobial activity against strains tested.


Asunto(s)
Aditivos Alimentarios/farmacología , Alcohol Feniletílico/análogos & derivados , Riboflavina/farmacología , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Sinergismo Farmacológico , Peróxido de Hidrógeno/química , Radical Hidroxilo/química , Alcohol Feniletílico/química , Alcohol Feniletílico/farmacología
20.
Gene ; 766: 145134, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32898605

RESUMEN

BACKGROUND: Artesunate (ART) has been used extensively as anti-malarial drugs worldwide. Besides, it has also been reported to have anti-cancer activities. This study was aimed to explore the anti-cancer activity of ART in combination with cisplatin (CIS) on A549 cells. METHODS: Cells were cultured with different concentrations of ART and/or CIS for 24, 48, or 72 h to test the anti-proliferative effects by CCK-8 assay. Colony formation assay and EdU staining were also performed. TUNEL staining was used to illustrate the morphologic changes. Cell cycle and apoptosis were determined by flow cytometry assay, and Western blot analysis was conducted to detect the expression of apoptosis- and proliferation-related proteins. Caspase activities were determined by colorimetric assay kit. Moreover, the synergistic effect of ART with CIS in A549 cell xenograft model was also determined. RESULTS: ART significantly inhibited cell proliferation in dose- and time-dependent manners. Collectively, the combination treatment remarkably decreased colony formation rates and increased the rates of TUNEL-positive cells compared with mono-treatment. Mechanistically, the combination treatment influenced the expression of Bcl-2, Bax, p-P53, Caspase-3/7, Caspase-9, CyclinB1, P34, P21, and synergistically regulated the activity of P38/JNK/ERK1/2 MAPK pathway. In mice A549 xenograft tumors, the combination strategy significantly increased the anti-cancer efficacy of ART and CIS alone, consistent with the in vitro observations. CONCLUSIONS: ART exhibited significant anti-tumor effect on A549 cells and this efficiency could be enhanced by combination with CIS.


Asunto(s)
Antineoplásicos/farmacología , Artesunato/farmacología , Cisplatino/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Células A549 , Animales , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Ratones , Ratones Desnudos , Inhibidores de Proteínas Quinasas/farmacología
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