目的:转化生长因子-β(TGF-β)在不同癌症亚型的形成中起重要作用。有证据表明TGF-β途径促进致癌细胞特征,但也具有肿瘤抑制能力。酪氨酸激酶抑制剂尼洛替尼,达沙替尼,厄洛替尼,吉非替尼,依维莫司被批准为几种肿瘤实体的靶向治疗,包括头颈部鳞状细胞癌(HNSCC)。本研究旨在研究这些物质对HPV阴性和HPV阳性SCC细胞培养物中TGFβ1和TGF-β2型受体(TGFβR2)表达水平的影响。
方法:使用酶联免疫吸附测定(ELISA)在三种HNSCC细胞系中确定了TGFβ1和TGFβR2的表达模式(即HNSCC-11A,HNSCC-14C,和CERV196)。这些细胞与尼洛替尼孵育,达沙替尼,厄洛替尼,吉非替尼,和依维莫司(20μmol/l),并与化疗对照进行比较。在处理24、48、72和96小时后进行浓度水平的评估。
结果:与阴性对照相比,在所有测试的细胞培养物中发现TGFβ1和TGFβR2的表达水平的统计学显著变化(p<0.05)。用大多数测试的酪氨酸激酶抑制剂治疗后,检测到TGFβ-R2表达增加,而观察到TGFβ1的减少。添加依维莫司对TGFβR2和TGF-B1表达具有相反的作用。
结论:在所有培养的HNSCC细胞系中均检测到TGFβ1和TGFβR2的表达。尼洛替尼,达沙替尼,厄洛替尼,吉非替尼,和依维莫司在体外对TGFβ1和TGFβR2的表达水平有影响。
OBJECTIVE: Transforming growth factor-β (TGF-β) plays a significant role in the formation of different cancer subtypes. There is evidence that TGF-β pathways promote cancerogenic cell characteristics but also have tumor-suppressor capabilities. The tyrosine kinase inhibitors nilotinib, dasatinib, erlotinib, gefitinib, and everolimus are approved as targeted therapies for several tumor entities, including head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate the effects of these substances on the expression levels of TGFβ1 and TGF-β receptor type 2 (TGFβR2) in HPV-negative and HPV-positive SCC cell cultures.
METHODS: Expression patterns of TGFβ1 and TGFβR2 were determined using enzyme-linked immunosorbent assay (ELISA) in three HNSCC cell lines (i.e., HNSCC-11A, HNSCC-14C, and CERV196). These cells were incubated with nilotinib, dasatinib, erlotinib, gefitinib, and everolimus (20 μmol/l) and compared to a chemonaive control. An assessment of concentration levels was conducted after 24, 48, 72, and 96 h of treatment.
RESULTS: Statistically significant changes in the expression levels of TGFβ1 and TGFβR2 were found in all tested cell cultures (p<0.05) compared to the negative control. An increase in TGFβ-R2 expression was detected after treatment with most of the tested tyrosine kinase inhibitors, whereas a reduction in TGFβ1 was observed. The addition of everolimus had the opposite effect on both TGFβR2 and TGF-B1- expression.
CONCLUSIONS: Expression of TGFβ1 and TGFβR2 was detected in all cultured HNSCC cell lines. Nilotinib, dasatinib, erlotinib, gefitinib, and everolimus had an impact on the expression levels of TGFβ1 and TGFβR2 in vitro.