ABSTRACT
OBJECTIVE@#To explore the mechanisms underlying the proliferative inhibition of Chinese herbal medicine Kang-Ai injection (KAI) in gastric cancer cells.@*METHODS@#Gastric cancer cell lines MGC803 and BGC823 were treated by 0, 0.3%, 1%, 3% and 10% KAI for 24, 48 and 72 h, respectively. The cell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The apoptosis and cell cycle were evaluated by flow cytometry. Interleukin (IL)-6 mRNA and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA), respectively. The protein expression levels of cyclin A, cyclin E, cyclin B1, cyclin D1, p21, retinoblastoma (RB), protein kinase B (AKT), extracellular regulated protein kinases (ERK), signal transducer and activator of transcription (STAT) 1 and STAT3 were detected by Western blot.@*RESULTS@#KAI inhibited the proliferation of MGC803 and BGC823 gastric cancer cells in dose- and time-dependent manner. After treated with KAI for 48 h, the proportion of G1 phase was increased, expression level of cyclin D1 and phosphorylation-RB were down-regulated, whereas the expression of p21 was up-regulated (all P<0.01). Furthermore, 48-h treatment with KAI decreased the phosphorylation level of STAT3, inhibited the mRNA and protein expressions of IL-6 (all P<0.01). IL-6 at dose of 10 ng/mL significantly attenuated the proliferative effect of both 3% and 10% KAI, and recovered KAI-inhibited STAT3 phosphorylation and cyclin D1 expression level (all P<0.01).@*CONCLUSION@#KAI exerted an anti-proliferative function by inhibiting IL-6/STAT3 signaling pathway followed by the induction of G1 phase arrest in gastric cancer cells.
Subject(s)
Humans , Apoptosis , Cell Line, Tumor , Cell Proliferation , Cyclin D1/pharmacology , Interleukin-6/metabolism , RNA, Messenger/metabolism , STAT3 Transcription Factor/metabolism , Stomach Neoplasms/geneticsABSTRACT
AbstractFucoidan, a sulfated polysaccharide found in marine algae and brown seaweeds, has been shown to inhibit the in vitro growth of human cancer cells. This study was conducted in cultured human bladder cancer EJ cells to elucidate the possible mechanisms by which fucoidan exerts its anti-proliferative activity, which until now has remained poorly understood. Fucoidan treatment of EJ cells resulted in dose-dependent inhibition of cell growth and induced apoptotic cell death. Flow cytometric analysis revealed that fucoidan led to G1 arrest in cell cycle progression. It was associated with down-regulation of cyclin D1, cyclin E, and cyclin-dependent-kinases (Cdks) in a concentration-dependent manner, without any change in Cdk inhibitors, such as p21 and p27. Furthermore, dephosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB with the transcription factors E2F-1 and E2F-4. Overall, our results demonstrate that fucoidan possesses anticancer activity potential against bladder cancer cells by inhibiting pRB phosphorylation.
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Objective To establish a model to predict the cell-cycle process in response to ionizing radiation.Methods Human choroidal malignant melanoma 92-1 cells were used and the cell cycle distribution of cells was analyzed in 0-96 h after exposure to X-rays.A phenomenological model was constructed based on biological knowledge to describe the cell cycle dynamics in experiments.Results In the present study,a phenomenological model was constructed to describe the cellcycle dynamics of synchronized 92-1 cells in responding to various doses of ionizing radiation.The simulation results obtained with the model were consistent with the experimental data,demonstrating that the model had a good expansibility and could be used to predict the dynamics of cell cycle in responding to ionizing radiation.Further theoretical modeling of the cellcycle dynamics was made and the results were consistent with the simulation.Conclusions A phenomenological model was constructed which could be used to describe the dynamics of cell cycle of cells exposed to ionizing radiation and was supported by the experimental data.Because this model is easy to run by the written code,it has a good expansibility for studying the behaviors of cell populations under various conditions.
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Objective To study the effects of the cytotoxicity, cell cycle and time dependent apoptosis of Jurkat T lymphoma cells induced by Tripterygium Hypoglaucum (Levl) Hutch (THH) alkaloids so ad to explore the mechanisms of the apoptosis induced by the THH alkaloids. Methods Cell vitality and cell proliferation were measured by Typan blue staining. Cell cycle and the time dependent apoptosis were determined by DNA staining, TUNEL labeling and flow cytometry. Results THH alkaloids could effectively inhibit cell proliferation of Jurkat cells and induce the G 1 arrest and could induce apoptosis in G 2/S phase first and then G 1 phase. Conclusion THH alkaloids can inhibit DNA synthesis, cell proliferation and can also induce apoptosis of Jurkat T lymphoma cells in all phases.