The importance of the role of fibroblasts in cancer microenvironment is well-recognized. However, the relationship between fibroblasts and asbestos-induced lung cancer remains underexplored. To investigate the effect of the asbestos-related microenvironment on lung cancer progression, lung cancer cells (NCI-H358, Calu-3, and A549) were cultured in media derived from IMR-90 lung fibroblasts exposed to 50 mg/L asbestos (chrysotile, amosite, and crocidolite) for 24 h. The kinetics and migration of lung cancer cells in the presence of asbestos-exposed lung fibroblast media were monitored using a real-time cell analysis system. Proliferation and migration of A549 cells increased in the presence of media derived from asbestos-exposed lung fibroblasts than in the presence of media derived from normal lung fibroblasts. We observed no increase in proliferation and migration in lung cancer cells cultured in asbestos-exposed lung cancer cell medium. In contrast, increased proliferation and migration in lung cancer cells exposed to media from asbestos-exposed lung fibroblasts was observed for all types of asbestos. Media derived from lung fibroblasts exposed to other stressors, such as hydrogen peroxide and UV radiation didn’t show as similar effect as asbestos exposure. An enzyme-linked immunosorbent assay (ELISA)-based cytokine array identified interleukin (IL)-6 and IL-8, which show pleiotropic regulatory effects on lung cancer cells, to be specifically produced in higher amounts by the three types of asbestos-exposed lung fibroblasts than normal lung fibroblasts. Thus, the present study demonstrated that interaction of lung fibroblasts with asbestos may support the growth and metastasis of lung cancer cells and that chrysotile exposure can lead to lung cancer similar to that caused by amphibole asbestos (amosite and crocidolite).
Broad industrial application of zeolites increases the opportunity of inhalation. However, the potential impact of different type and composition of zeolite on the cytotoxicity is still unknown. Four types of synthetic zeolites with have been prepared for assessing the effect on lung fibroblast: two zeolite L (LTL-R and LTL-D, ZSM-5 (MFI-S), and faujasite (FAU-S). The cytotoxicity of zeolites on human lung fibroblast (IMR-90) was assessed using WST1 cell proliferation assay, mitochondrial function, membrane leakage of lactate dehydrogenase, reduced glutathione levels, and mitochondrial membrane potential were assessed under control. Intracellular changes were examined using transmission electron microscopy (TEM). Toxicity related gene expression were evaluated by PCR array. The result showed a significantly higher toxicity in IMR-90 cells with FAU-S than LTL-R, LTL-D and MFI-S exposure. TEM showed FAU-S, spheroidal zeolite with a low Si/Al ratio, was readily internalized forming numerous phagosomes in IMR-90 cells, while the largest and disc-shaped zeolites showed the lowest toxicity and were located in submembranous phagosomes in IMR-90 cells. Differential expression of TNF related genes was detected using PCR arrays and confirmed using qRT-PCR analysis of selected genes. Collectively, the exposure of different zeolites shows different toxicity on IMR-90 cells.
To study the protective effects of radix astragali against anoxic damages to in vitro cultured neurons in rats, NaCN was used to develop a hypoxic model of in vitro cultured neurons from newborn rat cerebral cortex. The cellular morphology, A value (cell survival number) and effluxes of lactate dehydrogenase (LDH) and K+ from cells were measured in the radix astragali group and the control group respectively. After 48 h of anoxia, A value was decreased from 0.325 +/- 0.031 before anoxia to 0.145 +/- 0.011, the effluxes of LDH and K+ were increased from 65.80 +/- 2.90 U/L and 5. 23 +/- 0.11 mmol/L before anoxia to 148.80 +/- 8.40 U/L and 7.31 +/- 0.18 mmol/L, respectively. It was found that in the anoxic circumstance in the Radix astragali group, the mophological changes were mild, the effluxes of LDH and K+ were decreased and A value increased as compared with those in the control group. It was suggested that Radix astragali could protect the cultured rat neurons against anoxic damages in the anoxic circumstance.
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