The effects and mechanisms of berberine on proliferation of papillary thyroid cancer K1 cells induced by high glucose

Abstract

Objective: To study the effect and mechanisms of berberine (BBR) on the proliferation of papillary thyroid cancer K1 cells induced by high glucose. Methods: 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. Results: 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 P<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 P<0.05], and suppressed the expression of PI3K, p-Akt/Akt, Nrf2, and Nrf2 nuclear distribution (P<0.05). Conclusions: 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.