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The purpose of this study was to investigate the effect of Huaier extract supernatant(HES) on the proliferation, apoptosis, autophagy, and migration of human gastric cancer HGC-27 and MGC-803 cells and its molecular mechanisms. The main components in HES were preliminarily analyzed by high-performance liquid chromatography-mass spectrometry(HPLC-MS). Methyl thiazolyl tetrazolium(MTT) assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine(EdU) staining assay were used to explore the effect of HES on the proliferation of human gastric cancer HGC-27 and MGC-803 cells. Hoechst staining and flow cytometry assay were used to determine the effect of HES on apoptosis of human gastric cancer HGC-27 and MGC-803 cells. Acridine orange staining and cell scratch assay were used to determine the effect of HES on autophagy and migration of human gastric cancer HGC-27 and MGC-803 cells, respectively. Western blot was used to investigate the regulatory effect of HES on the expression levels of proteins related to apoptosis, epithelial-mesenchymal transition(EMT), and signaling pathways in human gastric cancer HGC-27 and MGC-803 cells. The results showed that HES mainly contained some components with high polarities. HES significantly reduced the cell viability of human gastric cancer cells in a dose-and time-dependent manner. The IC_(50 )values after 48 h of HES treatment in human gastric cancer HGC-27 and MGC-803 cells were 7.56 and 10.77 g·L~(-1), respectively. Meanwhile, HES inhibited the colony-forming ability and short-term proliferation of human gastric cancer cells. The apoptosis rates of HGC-27 and MGC-803 cells treated with 8 g·L~(-1) HES for 72 h were 62.13%±8.92% and 54.50%±3.26%, respectively. HES also promoted autophagy in human gastric cancer cells and impaired their migration ability in vitro. Moreover, HES up-regulated the cleavage of the apoptosis marker poly ADP-ribose polymerase(PARP) and the protein expression level of the epithelial cell marker E-cadherin, and down-regulated the protein levels of phosphorylated-mammalian target of rapamycin(p-mTOR), phosphorylated-S6(p-S6), and phosphorylated-extracellular signal-regulated kinase(p-ERK) in human gastric cancer cells. Therefore, HES is one of the effective anti-tumor components of Huaier, which inhibits the proliferation and migration of human gastric cancer cells, and induces apoptosis and autophagy. Moreover, the mTOR signal and ERK signal may be involved in the anti-gastric cancer effect of HES. This study provides novel references for the in-depth research and clinical application of Huaier. It is also of great significance to promote the scientific development and utilization of Huaier.
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Neoplasias Gástricas , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Gástricas/patologia , Apoptose , Serina-Treonina Quinases TOR/metabolismoRESUMO
As a traditional Chinese medicine, Chinese dragon's blood has multiple effects, such as activating blood to remove blood stasis, softening and dispelling stagnation, astringent and hemostasis, clearing swelling and relieving pain, regulating menstruation and rectifying the blood, so it is called "an effective medicine of promoting blood circulation". It has been widely used clinically to treat a variety of diseases. With the further research on Chinese dragon's blood, its anti-tumor medicinal value is gradually emerging. Modern pharmacological studies have shown that Chinese dragon's blood exerts anti-tumor effects mainly by inhibiting cell proliferation, inducing apoptosis, inducing DNA damage and cell cycle arrest, inducing senescence and autophagy of tumor cells, inhibiting metastasis and angiogenesis, as well as reversing multidrug resistance. This article focuses on the research progress on anti-tumor effects of Chinese dragon's blood extract and its chemical components, with a view to provide new references for the in-depth research and reasonable utilization of Chinese dragon's blood.
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Dracaena , China , Feminino , Extratos Vegetais , Resinas VegetaisRESUMO
This study aims to investigate the effect of Huaier aqueous extract on the growth and metastasis of human non-small cell lung cancer NCI-H1299 cells and its underlying mechanisms. MTT assay was used to detect the effect of Huaier aqueous extract on the proliferation of NCI-H1299 cells. Flow cytometry was used to examine the effect of Huaier aqueous extract on the apoptosis, cell cycle, and ROS level of NCI-H1299 cells. Wound healing assay was used to evaluate the effect of Huaier aqueous extract on the migration ability of NCI-H1299 cells. Western blot was used to detect the levels of proteins involving apoptosis, epithelial-mesenchymal transition(EMT), and MAPK signaling pathway in NCI-H1299 cells exposed to Huaier aqueous extract. The results showed that Huaier aqueous extract inhibited the proliferation of NCI-H1299 cells, and induced cell-cycle arrest at the phase S. Huaier aqueous extract promoted the apoptosis of NCI-H1299 cells by down-regulating the expression of anti-apoptotic protein Bcl-2. Moreover, Huaier aqueous extract increased ROS level and induced ferroptosis in NCI-H1299 cells. EMT played a critical role in cancer metastasis. Huaier aqueous extract reduced the migration ability of NCI-H1299 cells by inhibiting EMT of NCI-H1299 cells. In addition, this study revealed that Huaier aqueous extract inhibited MAPK signaling pathway in human non-small cell lung cancer NCI-H1299 cells, which may be one of Huaier's mechanisms in inhibiting growth and metastasis of NCI-H1299 cells. This study provides a new theoretical basis for the clinical treatment of lung cancer with Huaier, and important reference significance for further studies on the anti-tumor mechanisms of Huaier.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Misturas Complexas , Humanos , TrametesRESUMO
Silkworm cocoon was recorded to cure carbuncle in the Compendium of Materia Medica. Previous studies have demonstrated that the supplemental silk protein sericin exhibits anticancer activity. In the present study, we investigated the effects of silk fibroin peptide (SFP) extracted from silkworm cocoons against human lung cancer cells in vitro and in vivo and its possible anticancer mechanisms. SFP that we prepared had high content of glycine (~ 30%) and showed a molecular weight of ~ 10 kDa. Intragastric administration of SFP (30 g/kg/d) for 14 days did not affect the weights, vital signs, routine blood indices, and blood biochemical parameters in mice. MTT assay showed that SFP dose-dependently inhibited the growth of human lung cancer A549 and H460 cells in vitro with IC50 values of 9.921 and 9.083 mg/mL, respectively. SFP also dose-dependently suppressed the clonogenic activity of the two cell lines. In lung cancer H460 xenograft mice, intraperitoneal injection of SFP (200 or 500 mg/kg/d) for 40 days significantly suppressed the tumor growth, but did not induce significant changes in the body weight. We further examined the effects of SFP on cell cycle and apoptosis in H460 cells using flow cytometry, which revealed that SFP-induced cell cycle arrest at the S phase, and then promoted cell apoptosis. We demonstrated that SFP (20-50 mg/mL) dose-dependently downregulates Bcl-2 protein expression and upregulates Bax protein in H460 cells during cell apoptosis. The results suggest that SFP should be studied further as a novel therapeutic agent for the treatment of lung cancer.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Fibroínas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Peptídeos/farmacologia , Células A549 , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Fibroínas/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/química , Relação Estrutura-AtividadeRESUMO
Recently, red blood cell (RBC) membrane-coated nanoparticles have attracted much attention because of their excellent immune escapability; meanwhile, gold nanocages (AuNs) have been extensively used for cancer therapy due to their photothermal effect and drug delivery capability. The combination of the RBC membrane coating and AuNs may provide an effective approach for targeted cancer therapy. However, few reports have shown the utilization of combining these two technologies. Here, we design erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy. First, anti-EpCam antibodies were used to modify the RBC membranes to target 4T1 cancer cells. Second, the antitumor drug paclitaxel (PTX) was encapsulated into AuNs. Then, the AuNs were coated with the modified RBC membranes. These new nanoparticles were termed EpCam-RPAuNs. We characterized the capability of the EpCam-RPAuNs for selective tumor targeting via exposure to near-infrared irradiation. The experimental results demonstrate that EpCam-RPAuNs can effectively generate hyperthermia and precisely deliver the antitumor drug PTX to targeted cells. We also validated the biocompatibility of the EpCam-RAuNs in vitro. By combining the molecularly modified targeting RBC membrane and AuNs, our approach provides a new way to design biomimetic nanoparticles to enhance the surface functionality of nanoparticles. We believe that EpCam-RPAuNs can be potentially applied for cancer diagnoses and therapies.
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Nasopharyngeal carcinoma (NPC) occurs with high frequency in Asian populations, especially among people of Cantonese ancestry. In areas with high incidence, NPC clusters in families, which suggests that both geography and genetics may influence disease risk. Although the HLA-Bw46 locus is associated with increased risk of NPC, no predisposing genes have been identified so far. Here we report the results of a genome-wide search carried out in families at high risk of NPC from Guangdong Province, China. Parametric analyses provide evidence of linkage to the D4S405 marker on chromosome 4 with a logarithm of odds for linkage (lod) score of 3.06 and a heterogeneity-adjusted lod (hlod) score of 3.21. Fine mapping with additional markers flanking D4S405 resulted in a lod score of 3.54 and hlod score of 3.67 for the region 4p15.1-q12. Multipoint nonparametric linkage analysis gives lod scores of 3.54 at D4S405 (P = 5.4 x 10(-5)) and 4.2 at D4S3002 (P = 1.1 x 10(-5)), which is positioned 4.5 cM away from D4S405. When Epstein Barr virus antibody titer was included as a covariate, the lod scores reached 4.70 (P = 2.0 x 10(-5)) and 5.36 (P = 4.36 x 10(-6)) for D4S405 and D4S3002, respectively. Our findings provide evidence of a major susceptibility locus for NPC on chromosome 4 in a subset of families.
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Carcinoma/genética , Cromossomos Humanos Par 4 , Ligação Genética , Neoplasias Nasofaríngeas/genética , Adulto , Povo Asiático/genética , Carcinoma/virologia , China , Cromossomos Humanos Par 12 , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Genoma Humano , Herpesvirus Humano 4 , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/virologia , Linhagem , Recombinação GenéticaRESUMO
OBJECTIVE: To evaluate the relationship between overweight, obesity and arterial stiffness in community residents. METHODS: A total of 4585 community-dwelling adults in Jiangsu province, China were surveyed with the method of stratified and cluster sampling from 2007 to 2009. Overweight and obesity were defined by body mass index (BMI) and arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). Statistical analysis of arteriosclerosis included multivariate logistic regression testing among which BMI was viewed as continuous variable (1 kg/m(2) increasing to BMI) and categorical variables (underweight, normal, overweight and obesity) respectively. Odds ratio, population attributable risk percent and the optimal cut-off points for BMI to evaluate arteriosclerosis were analyzed using receiver operator characteristic (ROC) curve. RESULTS: (1) After age control, BMI of male or female were positively correlated with baPWV (r = 0.213, P < 0.01; r = 0.186, P < 0.01). baPWV and prevalence of arteriosclerosis were significantly higher in obese residents compared with normal body weight group (all P < 0.01). (2) As a continuous variable, the odds ratio value of BMI on predicting arteriosclerosis was 1.146 (95%CI: 1.117 - 1.175, P < 0.01) after adjusting of age, gender and hypertension. As categorical variables, the odds ratio value of BMI was 0.369 (95%CI: 0.141 - 0.962, P < 0.05) for underweight group, 1.576 (95%CI: 1.333 - 1.863) for overweight group and 2.087 (95%CI: 1.615 - 2.698) for obesity group (all P < 0.01). (3) The population attributable arteriosclerosis risk was 19.1% and 11.6% in overweight and obesity groups, respectively. The area under the ROC curve was 0.661 (95%CI: 0.645 - 0.678, P < 0.01) and the optimal cut-off point for BMI to evaluate arteriosclerosis was 24.25 kg/m(2). CONCLUSIONS: Overweight and obese residents faced higher risk for arteriosclerosis than normal population. Overweight and obesity are independent risk factors for arteriosclerosis after adjusting for age, gender and hypertension.
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Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Rigidez Vascular , Adulto , Idoso , Índice Tornozelo-Braço , Arteriosclerose , Velocidade do Fluxo Sanguíneo , Índice de Massa Corporal , China , Feminino , Humanos , Hipertensão , Masculino , Obesidade/complicações , Sobrepeso/complicações , Prevalência , Fluxo Pulsátil , Análise de Onda de Pulso , MagrezaRESUMO
In the structure of the title compound, C(18)H(15)ClN(4)O(4)S, the dihedral angle between the two benzene rings is 1.4â (3)°. The angle between the phenyl ring and thia-diazole ring is 5.8â (4)°. The conformations of the N-H and C=O bonds are anti with respect to each other. In the crystal structure, mol-ecules are linked by inter-molecular O-Hâ¯N, N-Hâ¯O and O-Hâ¯O hydrogen bonds, forming a three-dimensional network.
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Transcription regulation caused by global regulators exerts important effects on fungal secondary metabolism. By overexpression of the global regulator Talae1 in a Ficus elastica-associated fungus Trichoderma afroharzianum, two structurally new polyketides (1 and 2) that were newly produced in the transformant were isolated and identified. Their structures, including the absolute configurations, were elucidated through a combination of high resolution mass spectrometer (HRMS), NMR, and electronic circular dichroism (ECD) calculations. The growth inhibitory activities of compounds 1 and 2 were evaluated against four bacteria and six plant-pathogenic fungi. Compound 1 showed the highest antifungal activity against Botrytis cinerea and Fusarium oxysporum f. sp. nicotianae with MIC of 8 µg/ml. To the best of our knowledge, this is the first study to report on the application of the global regulator in T. afroharzianum to activate the biosynthesis of bioactive secondary metabolites.
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In this paper, we comprehensively evaluated the capability of imidazole-zinc reverse stain (ZN) in comparative proteomics. Three commonly used protein gel staining methods, including silver (SN), SYPRO Ruby (SR), and CB stain were investigated alongside for comparison purpose. A transparency scanning procedure, which may deliver more even and contrasting gel images, was found best for documenting ZN stained gels. Our results showed that ZN was more sensitive than SN, SR, and CB. It may reveal as few as 1.8 ng of proteins in a gel. Moreover, ZN was found to provide a linear dynamic range of staining for revealing proteins up to 140 ng, and show an insignificant staining preference. To analyze a ZN stained 2-D gel image that generally comprises an apparent but even background, the Melanie 4 software was found more suitable than others. Furthermore, ZN demonstrated an equivalent or better MS compatibility than the other three staining methods. Intense and comprehensive MS profiles were frequently observed for ZN stained gel spots. Approximate two-third of ZN stained gel spots were successfully identified for protein identities. Taken together, our results suggest that the prompt, cost effective and versatile ZN is well suited for current proteomic researches.
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Imidazóis/química , Proteômica/métodos , Zinco/química , Eletroforese em Gel Bidimensional/métodosRESUMO
Aminopeptidase N (APN) is a zinc-dependent ectopeptidase which plays an important role in the invasion of metastatic tumors. In this study, we report the synthesis and in vitro enzyme inhibition assay of 1,3,4-thiadiazole scaffold compounds. These new compounds have potent inhibitory activities toward APN with IC50 values in the micromolar range.
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Antígenos CD13/antagonistas & inibidores , Inibidores de Proteases/síntese química , Inibidores de Proteases/farmacologia , Tiadiazóis/síntese química , Tiadiazóis/farmacologia , Indicadores e Reagentes , Leucina/análogos & derivados , Leucina/química , Leucina/farmacologia , Inibidores de Metaloproteinases de Matriz , Relação Estrutura-AtividadeRESUMO
In the structure of the title compound, C(17)H(13)BrN(4)O(2)S, the dihedral angle between the two benzene rings is 38.5â (1)°; the angle between the 4-bromo-benzene and thia-diazole rings is 1.3â (1)°. The conformations of the N-H and C=O bonds are anti with respect to each other. The structure displays inter-molecular N-Hâ¯O and C-Hâ¯O hydrogen bonding, with both interactions leading to inversion dimers.
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The precise diagnosis of cancer remains a great challenge; therefore, it is our research interest to develop safe, tumor-specific reagents. In this study, we designed nanovesicles derived from erythrocyte membranes; the nanovesicles are capable of recognizing tumor cells for both circulating tumor cell (CTC) capture and tumor imaging. The tumor-targeting molecules folic acid (FA) and fluorescein Cy5 were modified on the nanovesicle surface. The developed nanovesicles exhibit excellent tumor targeting ability both in vitro and in vivo for CTC capture and in tumor imaging. Compared with traditional immunomagnetic beads, the proposed nanovesicles are capable of avoiding non-specific adsorption as a derivative of red blood cells. Combined with a non-invasive means of micromanipulation, the nanometer-sized vesicles show a high purity of CTC capture (over 90%). In vivo, the nanovesicles can also be employed for efficient tumor imaging without obvious toxicity and side effects. In brief, the nanovesicles prepared herein show potential clinical application for integrated diagnosis in vitro and in vivo.
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Carbocianinas , Eritrócitos , Neoplasias Experimentais , Células Neoplásicas Circulantes/metabolismo , Imagem Óptica , Animais , Carbocianinas/química , Carbocianinas/farmacologia , Eritrócitos/química , Eritrócitos/metabolismo , Feminino , Células HCT116 , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/metabolismoRESUMO
Capturing circulating tumor cells (CTCs) from peripheral blood for subsequent analyses has shown potential in precision medicine for cancer patients. Broad as the prospect is, there are still some challenges that hamper its clinical applications. One of the challenges is to maintain the viability of the captured cells during the capturing and releasing processes. Herein, we have described a composite material that could encapsulate a magnetic Fe3O4 core in a MIL-100 shell (MMs), which could respond to pH changes and modify the anti-EpCAM antibody (anti-EpCAM-MMs) on the surface of MIL-100. After the anti-EpCAM-MMs captured the cells, there was no need for additional conditions but with the acidic environment during the cell culture process, MIL-100 could realize automatic degradation, leading to cell self-release. This self-release model could not only improve the cell viability, but could also reduce the steps of the release process and save human and material resources simultaneously. In addition, we combined clinical patients' case diagnosis with the DNA sequencing and next generation of RNA sequencing technologies in the hope of precision medicine for patients in the future.
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Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Estruturas Metalorgânicas/química , Células Neoplásicas Circulantes/metabolismo , Anticorpos Imobilizados/química , Anticorpos Imobilizados/imunologia , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Molécula de Adesão da Célula Epitelial/imunologia , Óxido Ferroso-Férrico/química , Humanos , Neoplasias Hepáticas/genética , Nanopartículas de Magnetita/química , Masculino , Pessoa de Meia-Idade , Mutação , Células Neoplásicas Circulantes/patologia , Transcriptoma , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
Although anti-PD-1 immunotherapy is widely used to treat melanoma, its efficacy still has to be improved. In this work, we present a therapeutic method that combines immunotherapy and starvation therapy to achieve better antitumor efficacy. We designed the CMSN-GOx method, in which mesoporous silica nanoparticles (MSN) are loaded with glucose oxidase (GOx) and then encapsulate the surfaces of cancer cell membranes to realize starvation therapy. By functionalizing the MSN's biomimetic surfaces, we can synthesize nanoparticles that can escape the host immune system and homologous target. These attributes enable the nanoparticles to have improved cancer targeting ability and enrichment in tumor tissues. Our synthetic CMSN-GOx complex can ablate tumors and induce dendritic cell maturity to stimulate an antitumor immune response. We performed an in vivo analysis of these nanoparticles and determined that our combined therapy CMSN-GOx plus PD-1 exhibits a better antitumor therapeutic effect than therapies using CMSN-GOx or PD-1 alone. Additionally, we used the positron emission tomography imaging to measuring the level of glucose metabolism in tumor tissues, for which we investigate the effect with the cancer therapy in vivo.
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Antineoplásicos/farmacologia , Membrana Celular/química , Imunoterapia , Melanoma Experimental/terapia , Nanopartículas/química , Dióxido de Silício/química , Animais , Membrana Celular/imunologia , Glucose Oxidase/química , Glucose Oxidase/imunologia , Glucose Oxidase/metabolismo , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Tamanho da Partícula , Porosidade , Dióxido de Silício/imunologia , Propriedades de Superfície , Células Tumorais CultivadasRESUMO
Both the aminopeptidase N (APN) and matrix metalloproteinase (MMP) are essential metallopeptidases in the development of tumor invasion and angiogenesis. A series of novel peptide-like derivatives were designed and synthesized as antitumor agents. Their structures were confirmed by IR, MS, and (1)H-NMR. These compounds exhibited potent inhibitory activities against APN and low activity against MMP in vitro. The derivatives with methoxy group show better activities than those with other substituted group and could be used as lead compounds for exploring new APN inhibitors in the future.
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Antígenos CD13/antagonistas & inibidores , Peptídeos/síntese química , Peptídeos/farmacologia , Inibidores de Proteases/síntese química , Inibidores de Proteases/farmacologia , Escherichia coli/química , Ligação de Hidrogênio , Espectrometria de Massas , Inibidores de Metaloproteinases de Matriz , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria InfravermelhoRESUMO
The asymmetric unit of the title compound, C(21)H(20)N(4)O(3)S, contains two independent mol-ecules. The dihedral angles between the two benzene rings are 47.6â (1) and 30.2â (1)°, the corresponding values between the p-methoxy-benzene and thia-diazol rings are 12.3â (1) and 24.7â (1)°, respectively, for the two mol-ecules. The conformations of the N-H and C=O bonds are anti with respect to each other. The enone groups show a trans configuration. The crystal structure is stabilized by N-Hâ¯O and N-Hâ¯N inter-actions. The absolute structure could not be determined from the X-ray data but the absolute configuration has been assigned by reference to an unchanging chiral centre in the synthetic procedure.
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In the title compound, C(20)H(17)ClN(4)O(2)S, the dihedral angle between the two benzene rings is 65.9â (1)°; the corresponding angle between the 4-chloro-phenyl and thia-diazole rings is 3.4â (8)°. The conformations of the N-H and C=O bonds are anti with respect to each other. The enone groups show a trans configuration. The structure displays intermolecular N-Hâ¯O, C-Hâ¯N, C-Hâ¯S and C-Hâ¯O hydrogen bonding.
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Swertia mussotii (Gentianaceae) is a traditional Chinese medicinal plant grown in the Qinghai-Tibet Plateau. Three fractions from S. mussotii extract, named SWF50, SWF 70 and SWF100, were screened for in vitro anti-proliferative activity on two gastric cancer cell lines, MGC-803 and BGC-823 cells using MTT assay. Our results demonstrated that SMF70 showed an anti-proliferative effect in MGC-803 cells and SMF100 showed an anti-proliferative effect in BGC-823 cells in vitro. Moreover, both two fractions induced apoptosis via depolymerization of cytoskeletal filaments, increased cytoplasmic levels of ROS and Ca2+ and disrupted mitochondrial transmembrane potential. In addition, flow cytometry analysis indicated that both two fractions could induce cell apoptosis and arrest the cell cycle at S phase. Our results indicate that SMF70 induces apoptosis of MGC-803 cells and SMF100 induces apoptosis of BGC-823 cells via a mitochondrial-dependent pathway. Meanwhile, we also investigated antitumor effect of SMF70 in vivo, and exhibited effective tumor growth inhibition. Our findings demonstrate that S. mussotii extracts could be a potential new alternative therapeutic agent gastric cancer.
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Apoptose/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Swertia/química , Linhagem Celular Tumoral , Gentianaceae/química , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Plantas Medicinais/química , Estômago/efeitos dos fármacosRESUMO
Filtration of circulating tumor cells (CTCs) in peripheral blood is of proven importance for early cancer diagnosis, treatment monitoring, metastasis diagnosis, and prognostic evaluation. However, currently available strategies for enriching CTCs, such as magnetic activated cell sorting (MACS), face serious problems with purity due to nonspecific interactions between beads and leukocytes in the process of capturing. In the present study, the tumor-targeting molecule folic acid (FA) and magnetic nanoparticles (MNPs) were coated on the surface of red blood cells (RBCs) by hydrophobic interaction and chemical conjugation, respectively. The resulting engineered RBCs rapidly adhered to CTCs and the obtained CTC-RBC conjugates were isolated in a magnetic field. After treatment with RBC lysis buffer and centrifugation, CTCs were released and captured. The duration of the entire process was less than three hours. Cell counting showed that the capture efficiency was above 90% and the purity of the obtained CTCs was higher than 75%. The performance of the proposed method exceeded that of MACS® beads (80% for capture efficiency and 20% for purity) under the same conditions. The obtained CTCs could be successfully re-cultured and proliferated in vitro. Our engineered RBCs have provided a novel method for enriching rare cells in the physiological environment.