Aim To investigate the antitumor activities and mechanisms of sodium rosmarinate against hepatocellu- lar carcinoma. Methods Antitumor activities of sodium rosmarinate were measured on HepG2, HNE, K562, HCT116, and SW...Aim To investigate the antitumor activities and mechanisms of sodium rosmarinate against hepatocellu- lar carcinoma. Methods Antitumor activities of sodium rosmarinate were measured on HepG2, HNE, K562, HCT116, and SW480 cells by MTT assay in vitro at 5 mg· L^-1, 25 mg · L^-1 , and 50 mg · L^-1. Nude mice and H22 cells were employed to establish a liver tumor-bearing murine model. Sodium rosmarinate were intraperitoneal- ly administered at 25 mg. kg^-1 and 50 mg · kg^-1 for 10 days. Body weights, organ indexes, white blood cells, lymphocytes, and neutrophils of peripheral blood were measured. Murine tumors were histologically stained. TNF- ot and IFN-γ in serum were detected by ELISA. Expressions of Caspase-3, Bcl-2, Bax, Sift1, NF-KB p65, NF-KB pS0, and p-IKB-ot were measured by realtime-PCR and Western blot. Results Sodium rosmarinate showed obvi- ous inhibition on proliferation of HepG-2 cells at 5 mg · L^-1 But no inhibition effects were observed on HNE K562, HCT116, and SW480 cells. Body weights and organ indexes of nude mice with H22 cells were not changed by sodium rosmarinate. But sodium rosmarinate showed significant inhibition rate at 25 mg · kg^-1（45.67% ） and 50 mg · kg ^-l （ 52. 82% ）. Necrosis was aggregated by sodium rosmarinate as shown by H＆E staining. TNF-α and IFN-γ in murine serum were significantly increased by sodium rosmarinate at both doses （P 〈 0.05）. Expressions of caspase-3 were significantly increased （P 〈 0.01 ）. Sodium rosmarinate were shown to increase expressions of Bax, decrease expressions of Bcl-2, and significantly decrease Bacl-2/Bax ratio to induce apoptosis. Expressions ofSirtl, NF-KB p65, NF-KB p50, and p-IKB-αwere all decreased dose-dependently. Discussion Sodium rosmari- hate were demonstrated to inhibit hepatocellular carcinoma in vivo and in vitro through up-regulating TNF-α, IFN- γ , Bcl-2/Bax ratio, and down-regulating Sirtl and NF-KB related genes dose dependently, which may be devel- oped a promising drug for treatment of hepatocellular carcinoma.展开更多
Sirt1(Sirtuin type 1)是依赖于烟酰胺腺嘌呤二核苷酸(NAD+)的组蛋白脱乙酰酶,为Sirtuins家族成员之一,与细胞增殖、分化、衰老、凋亡和代谢密切相关。目前,有关Sirt1与衰老和代谢的论文已在Science、Nature、Cell等杂志上连续刊出。其...Sirt1(Sirtuin type 1)是依赖于烟酰胺腺嘌呤二核苷酸(NAD+)的组蛋白脱乙酰酶,为Sirtuins家族成员之一,与细胞增殖、分化、衰老、凋亡和代谢密切相关。目前,有关Sirt1与衰老和代谢的论文已在Science、Nature、Cell等杂志上连续刊出。其中,Sirt1通过抑制PPARγ促进白色脂肪细胞中脂肪动员,并且通过下调肌细胞标志基因表达来抑制成肌细胞分化。提示Sirt1不仅是一个重要的与机体“长寿”有关的因子,而且可能在动物脂肪沉积和肌肉发育中起着关键的调控作用。展开更多
文摘Aim To investigate the antitumor activities and mechanisms of sodium rosmarinate against hepatocellu- lar carcinoma. Methods Antitumor activities of sodium rosmarinate were measured on HepG2, HNE, K562, HCT116, and SW480 cells by MTT assay in vitro at 5 mg· L^-1, 25 mg · L^-1 , and 50 mg · L^-1. Nude mice and H22 cells were employed to establish a liver tumor-bearing murine model. Sodium rosmarinate were intraperitoneal- ly administered at 25 mg. kg^-1 and 50 mg · kg^-1 for 10 days. Body weights, organ indexes, white blood cells, lymphocytes, and neutrophils of peripheral blood were measured. Murine tumors were histologically stained. TNF- ot and IFN-γ in serum were detected by ELISA. Expressions of Caspase-3, Bcl-2, Bax, Sift1, NF-KB p65, NF-KB pS0, and p-IKB-ot were measured by realtime-PCR and Western blot. Results Sodium rosmarinate showed obvi- ous inhibition on proliferation of HepG-2 cells at 5 mg · L^-1 But no inhibition effects were observed on HNE K562, HCT116, and SW480 cells. Body weights and organ indexes of nude mice with H22 cells were not changed by sodium rosmarinate. But sodium rosmarinate showed significant inhibition rate at 25 mg · kg^-1（45.67% ） and 50 mg · kg ^-l （ 52. 82% ）. Necrosis was aggregated by sodium rosmarinate as shown by H＆E staining. TNF-α and IFN-γ in murine serum were significantly increased by sodium rosmarinate at both doses （P 〈 0.05）. Expressions of caspase-3 were significantly increased （P 〈 0.01 ）. Sodium rosmarinate were shown to increase expressions of Bax, decrease expressions of Bcl-2, and significantly decrease Bacl-2/Bax ratio to induce apoptosis. Expressions ofSirtl, NF-KB p65, NF-KB p50, and p-IKB-αwere all decreased dose-dependently. Discussion Sodium rosmari- hate were demonstrated to inhibit hepatocellular carcinoma in vivo and in vitro through up-regulating TNF-α, IFN- γ , Bcl-2/Bax ratio, and down-regulating Sirtl and NF-KB related genes dose dependently, which may be devel- oped a promising drug for treatment of hepatocellular carcinoma.
文摘Sirt1(Sirtuin type 1)是依赖于烟酰胺腺嘌呤二核苷酸(NAD+)的组蛋白脱乙酰酶,为Sirtuins家族成员之一,与细胞增殖、分化、衰老、凋亡和代谢密切相关。目前,有关Sirt1与衰老和代谢的论文已在Science、Nature、Cell等杂志上连续刊出。其中,Sirt1通过抑制PPARγ促进白色脂肪细胞中脂肪动员,并且通过下调肌细胞标志基因表达来抑制成肌细胞分化。提示Sirt1不仅是一个重要的与机体“长寿”有关的因子,而且可能在动物脂肪沉积和肌肉发育中起着关键的调控作用。
