Ni J, Wang F, Yue L, Xiang G D, Zhao L S, Wang Y, Ye L Z, Dong J
Department of Endocrinology in Wuhan General Hospital of Chinese People's Liberation Army, Wuhan 430070, China.
Zhonghua Nei Ke Za Zhi. 2017 Jul 1;56(7):507-511. doi: 10.3760/cma.j.issn.0578-1426.2017.07.007.
To study the effect and mechanisms of berberine (BBR) on the proliferation of papillary thyroid cancer K1 cells induced by high glucose. K1 cells were cultured under 5.5 mmol/L or 25 mmol/L glucose condition with or without different concentration of BBR (0, 10, 40 and 80 μmol/L) for 24 hours. The proliferations of K1 cells in each condition were detected by MTT. Western blot was used to measure the expression of nuclear factor erythroid 2-related factor 2(Nrf2), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt) and phosphorylated-Akt (p-Akt). The distribution pattern of Nrf2 in K1 cells was determined using immunofluorescent staining. Compared with 5.5 mmol/L condition, the proliferation rate [(126.64±5.41) % vs (87.31±3.67)%], expression levels of PI3K (0.425±0.019 vs 0.272±0.039), p-Akt/Akt (0.446±0.021 vs 0.168±0.035) and Nrf2 (0.597±0.014 vs 0.308±0.026), and Nrf2 distribution (93.0% vs 23.1%) in nuclear of K 1 cells under 25 mmol/L condition were significantly elevated, respectively (all <0.01). Addition of BBR in 25 mmol/L condition dose dependently (10, 40, 80 μmol/L) lowered the proliferation rate of K1 cells [(111.76±4.10)%, (70.03±2.18)%, (32.41±3.76)% vs (126.64±5.41)%, all <0.05], and suppressed the expression of PI3K, p-Akt/Akt, Nrf2, and Nrf2 nuclear distribution (<0.05). BBR dose dependently inhibited the proliferation of high glucose-induced K1 cells. This effect was associated with the suppression on of PI3K/Akt signaling activation, Nrf2 expression and its nuclear translocation.
研究小檗碱（BBR）对高糖诱导的甲状腺乳头状癌K1细胞增殖的影响及其机制。将K1细胞在5.5 mmol/L或25 mmol/L葡萄糖条件下，分别加入不同浓度的BBR（0、10、40和80 μmol/L）培养24小时。采用MTT法检测各条件下K1细胞的增殖情况。用蛋白质免疫印迹法检测核因子E2相关因子2（Nrf2）、磷酸肌醇3激酶（PI3K）、蛋白激酶B（Akt）和磷酸化Akt（p-Akt）的表达。用免疫荧光染色法检测K1细胞中Nrf2的分布模式。与5.5 mmol/L条件相比，25 mmol/L条件下K1细胞的增殖率[（126.64±5.41）%对（87.31±3.67）%]、PI3K表达水平（0.425±0.019对0.272±0.039）、p-Akt/Akt（0.446±0.021对0.168±0.035）和Nrf2（0.597±0.014对0.308±0.026）以及K1细胞核内Nrf2分布（93.0%对23.1%）均显著升高（均P<0.01）。在25 mmol/L条件下加入BBR呈剂量依赖性（10、40、80 μmol/L）降低K1细胞的增殖率[（111.76±4.10）%、（70.03±2.18）%、（32.41±3.76）%对（126.64±5.41）%，均P<0.05]，并抑制PI3K、p-Akt/Akt、Nrf2的表达及Nrf2的核分布（P<0.05）。BBR呈剂量依赖性抑制高糖诱导的K1细胞增殖。这一作用与抑制PI3K/Akt信号激活、Nrf2表达及其核转位有关。
