Candida albicans Beta-Glucan Induce Anti- Cancer Activity of Mesenchymal Stem Cells against Lung Cancer Cell Line: An In-Vitro Experimental Study.
- 作者列表："Peymaeei F","Sadeghi F","Safari E","Khorrami S","Falahati M","Roudbar Mohammadi S","Roudbary M
OBJECTIVE:β-glucan, glucopyranosyl polymers of fungi cell wall, represent an immune stimulating effects with potential anti-cancer activity. Mesenchymal stem cells (MSC) have immunomodulating properties in cancer microenvironment. The aim of this study was to investigate the anti-cancer effect of Candida albicans (C. albicans) beta-glucan on MSCs supernatant for apoptosis assay of lung cancer cells in vitro. METHODS:Beta-glucan was extracted from cell wall of C.albicans. MSC isolated from adipose tissue of patients and confirmed using specific surface markers expression which examined by flow cytometry. MSCs treated with various concentrations of β-glucans for 48 hours. Cytotoxic effect of β-glucans was evaluated using MTT assay. MSC and lung cancer line cocultured and treated with β-glucans and apoptosis assay was done by flow cytometry. RESULTS:Cytotoxicity findings showed a significant decrease in MSC viability during 48h, however it was dose-dependent (P<0.05). According to the obtained findings, supernatant of mesenchymal stem cells treated with β-glucans increased cancer cells apoptosis (P<0.05). CONCLUSION:Beta glucan may highlight a potential and novel promising candidate in future strategies to cause apoptosis of cancer cells and consider as therapeutic agent against tumor growth as well. Definitely, more in vitro and in vivo studies are required to understand its functions.
目的: β-葡聚糖，真菌细胞壁的吡喃葡萄糖基聚合物，代表了具有潜在抗癌活性的免疫刺激作用。间充质干细胞 (MSC) 在癌症微环境中具有免疫调节特性。本研究的目的是探讨白念珠菌 β-葡聚糖对骨髓间充质干细胞上清液的抗癌作用，用于体外检测肺癌细胞的凋亡。 方法: 从白色念珠菌细胞壁中提取 β-葡聚糖。从患者的脂肪组织分离MSC，并使用通过流式细胞术检查的特异性表面标记物表达来确认。用不同浓度的 β-葡聚糖处理MSCs 48 小时。使用MTT测定法评价 β-葡聚糖的细胞毒性作用。MSC和肺癌细胞系共培养并用 β-葡聚糖处理，并通过流式细胞术进行细胞凋亡测定。 结果: 细胞毒性结果显示，在 48 小时内MSC活力显著降低，但呈剂量依赖性 (P<0.05)。根据所得结果，经 β-葡聚糖处理的间充质干细胞上清液增加了癌细胞凋亡 (P<0.05)。 结论: β 葡聚糖可能在未来导致癌细胞凋亡的策略中突出一个潜在的和新的有前途的候选物，并考虑作为抗肿瘤生长的治疗剂。当然，需要更多的体外和体内研究来了解其功能。
METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.
METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.
METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.