Effect of arsenic trioxide in combination with cisplatin on the proliferation of glioma C6 cells
Wang Zhi-gan
Abstract
Wang Zhi-gan
Abstract
Objective To investigate the effects of arsenic trioxide in combination with cisplatin on the proliferation of glioma cells C6. Methods In the in vitro experiment, the proliferation inhibition of glioma cell line C6 was assessed by MTT assay, and the cell cycle distribution and apoptosis ratio of the cells were detected by flow cytometry. The expression levels of caspase-3, PTEN, PI3K and Akt were examined by Western blot. In the in vivo experiment, the expression levels of caspase-3 and IκB-α were measured by immunohistochemical methods, and the rats' life span was observed.Results At the dosage of 12.5 μmol/L of As2O3 and 10.0 μmol/L of CDDP, the proliferation inhibitory ratios of As2O3, CDDP andco-treatment group on glioma cell line C6 after 24 hours were 34.37%, 31.73% and 76.40%, respectively. Correspondingly, the apoptosis ratios after 24 hours were(4.60 ± 1.12)%,(14.59 ± 0.79)% and(36.13 ± 1.55)% respectively. Apoptosis induction was also proved by FACS using PI-stained method. The expression levels of caspase-3 and PTEN were up-regulated, while the expression levels of PI3K and Akt were down-regulated in the co-treatment group. For in vivo experiment, the expression of caspase-3 was up-regulated and IκB-α was down-regulated in the co-treatment group. However, the rats' survival rate in different treatment groups was similar in the limited observation time(P = 0.2531). Conclusion As2O3 combined with CDDP has potent inhibitory action on glioma cells proliferation through up-regulating caspase-3 and PTEN and down-regulating PI3K, Akt and IκB-α expression levels.
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Objective To investigate the effects of arsenic trioxide in combination with cisplatin on the proliferation of glioma cells C6. Methods In the in vitro experiment, the proliferation inhibition of glioma cell line C6 was assessed by MTT assay, and the cell cycle distribution and apoptosis ratio of the cells were detected by flow cytometry. The expression levels of caspase-3, PTEN, PI3K and Akt were examined by Western blot. In the in vivo experiment, the expression levels of caspase-3 and IκB-α were measured by immunohistochemical methods, and the rats' life span was observed.Results At the dosage of 12.5 μmol/L of As2O3 and 10.0 μmol/L of CDDP, the proliferation inhibitory ratios of As2O3, CDDP andco-treatment group on glioma cell line C6 after 24 hours were 34.37%, 31.73% and 76.40%, respectively. Correspondingly, the apoptosis ratios after 24 hours were(4.60 ± 1.12)%,(14.59 ± 0.79)% and(36.13 ± 1.55)% respectively. Apoptosis induction was also proved by FACS using PI-stained method. The expression levels of caspase-3 and PTEN were up-regulated, while the expression levels of PI3K and Akt were down-regulated in the co-treatment group. For in vivo experiment, the expression of caspase-3 was up-regulated and IκB-α was down-regulated in the co-treatment group. However, the rats' survival rate in different treatment groups was similar in the limited observation time(P = 0.2531). Conclusion As2O3 combined with CDDP has potent inhibitory action on glioma cells proliferation through up-regulating caspase-3 and PTEN and down-regulating PI3K, Akt and IκB-α expression levels.
Key concepts: Arsenic trioxide, Apoptosis, Glioma, PTEN, Cisplatin, PI3K/AKT/mTOR pathway, In vivo, Cell growth