背景:分子和细胞因子可以在癌症治疗中被靶向。转化生长因子-β(TGF-β)是一种作用于质膜中蛋白激酶受体的细胞因子。TGF-β信号通路可触发磷脂酰肌醇-4,5-二磷酸3-激酶(PI3K)通路,在癌症生长和发展中重要的信号转导途径。然而,这种PI3K/AKT级联可以被磷酸酶和张力蛋白同源物(PTEN)肿瘤抑制基因抑制。
目的:通过TGF-β/PI3K途径和PTEN抑癌基因,研究苦参素甲醇提取物(HSE)对乳腺癌(BC)小鼠模型的抑制作用。
方法:雌性C57BL6小鼠皮下注射1mg/kg体重(BW)的致癌物质DMBA,并喂养高脂饮食(HFD)。小鼠随机分为五组(n=6):阴性对照(NC)给予标准饮食,阳性对照(PC)给予DMBA和HFD,和三个治疗组(T1,T2和T3)用HSE剂量0.33,0.66和0.99g/kgBW治疗12周。通过ELISA评估小鼠血清中的TGF-β浓度,并通过qRT-PCR评估PIK3CA和PTEN基因表达。
结果:HSE治疗导致治疗组T1血清中TGF-β浓度显着降低(35.31±17.33),T2(43.31±17.42),与PC组(162.09±11.60)pg/mL相比,T3(48.67±20.94)pg/mL(p<0.001)。然而,只有剂量为0.99g/kgBW的HSE降低了PIK3CA基因的表达(p=0.026),在0.66g/kgBW的剂量下,PTEN的表达增加了4.93倍。
结论:HSE能够抑制TGF-β/PIK3CA通路并增加PTEN基因的表达。
BACKGROUND: Molecules and cytokines can be targeted in cancer therapy. Transforming growth factor-beta (TGF-β) is a cytokine that acts on protein kinase receptors in the plasma membrane. The signaling pathway of TGF-β can trigger the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway, a signal transduction pathway important in cancer growth and development. However, this PI3K/AKT cascade can be inhibited by phosphatase and tensin homolog (PTEN) tumor suppressor genes.
OBJECTIVE: To determine the inhibitory effect of
Holothuria scabra methanol extract (HSE) on breast cancer growth through the TGF-β/PI3K pathways and PTEN tumor suppressor gene on a breast cancer (BC) mice model.
METHODS: Female C57BL6 mice were subcutaneously injected with carcinogen DMBA 1 mg/kg body weight (BW) and fed a high-fat diet (HFD). Mice were randomly divided into five groups (n = 6): negative control (NC) administered with a standard diet, positive control (PC) administered with DMBA and HFD, and three treatment groups (T1, T2, and T3) treated with HSE doses of 0.33, 0.66, and 0.99 g/kg BW for 12 weeks. TGF-β concentration in the blood serum of mice was assessed by ELISA and the PIK3CA and PTEN gene expression by qRT-PCR.
RESULTS: The treatment with HSE resulted in a significant decrease in TGF-β concentrations in the blood sera of treatment groups T1 (35.31 ± 17.33), T2 (43.31 ± 17.42), and T3 (48.67 ± 20.94) pg/mL compared to the PC group (162.09 ± 11.60) pg/mL (p < 0.001). However, only HSE at a dose of 0.99 g/kg BW decreased the PIK3CA gene expression (p = 0.026), and at a dose of 0.66 g/kg BW increased the PTEN expression up to 4.93-fold.
CONCLUSIONS: HSE is capable of inhibiting the TGF-β/PIK3CA pathway and increasing the PTEN gene expression.