Three Departments of Abdominal Surgery, Xingtai First Hospital, No. 376 Shunde Road, Qiaodong District, Xingtai 054000, Hebei, China.
The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang 050000, Hebei, China.
Anticancer Agents Med Chem. 2022;22(3):596-602. doi: 10.2174/1871520621666210402110331.
Papillary Thyroid Carcinoma (PTC) represents the most common thyroid cancer. Until recently, treatment options for PTC patients are limited. Nilotinib is the second-generation tyrosine kinase inhibitor, and has been widely used in the treatment of Chronic Myeloid Leukemia (CML).
We aimed to explore whether nilotinib is effective for the suppression PTC cancer progression and the underlying mechanisms.
In this study, the three human PTC cell lines (KTC-1, BCPAP, and TPC1) were used to verify the effects of nilotinib on cell growth. The half maximal inhibitory concentration (IC50) was calculated according to the growth curve post nilotinib treatment at different concentrations. Cell counting kit-8 and colony formation analysis were used to monitor cell growth after nilotinib treatment. Cell apoptosis and autophagy related proteins and phosphorylation of PI3K/Akt/mTOR were detected by Western blotting analysis.
Nilotinib treatment could effectively inhibit PTC cell growth, which was accompanied by an increase in apoptosis and induction of autophagy. Mechanistically, nilotinib treatment repressed the phosphorylation of the PI3K/Akt/mTOR pathway.
Collectively, our results demonstrated that nilotinib may display anti-tumor effect against PTC via inhibiting PI3K/Akt/mTOR pathway and inducing apoptosis and autophagy.
甲状腺乳头状癌(PTC)是最常见的甲状腺癌。直到最近,PTC 患者的治疗选择仍然有限。尼洛替尼是第二代酪氨酸激酶抑制剂,已广泛用于治疗慢性髓性白血病(CML)。
我们旨在探讨尼洛替尼是否对抑制 PTC 癌症进展有效,以及其潜在机制。
在这项研究中,使用了三种人甲状腺乳头状癌细胞系(KTC-1、BCPAP 和 TPC1)来验证尼洛替尼对细胞生长的影响。根据尼洛替尼处理不同浓度后生长曲线计算半最大抑制浓度(IC50)。用细胞计数试剂盒-8 和集落形成分析监测尼洛替尼处理后的细胞生长。通过 Western blot 分析检测细胞凋亡和自噬相关蛋白以及 PI3K/Akt/mTOR 的磷酸化。
尼洛替尼处理可有效抑制 PTC 细胞生长,伴随凋亡增加和自噬诱导。从机制上讲,尼洛替尼处理抑制了 PI3K/Akt/mTOR 通路的磷酸化。
总的来说,我们的结果表明,尼洛替尼可能通过抑制 PI3K/Akt/mTOR 通路以及诱导凋亡和自噬对 PTC 发挥抗肿瘤作用。