Lin Bo, Lu Bing, Hsieh I-Yun, Liang Zhen, Sun Zicheng, Yi Yang, Lv Weiming, Zhao Wei, Li Jie
Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Institute of Urology of Shenzhen University, The Third Affiliated Hospital of Shenzhen University, Shenzhen Luohu Hospital Group, Shenzhen, China.
Front Pharmacol. 2020 May 13;11:632. doi: 10.3389/fphar.2020.00632. eCollection 2020.
Anaplastic thyroid cancer is the most aggressive thyroid cancer and has a poor prognosis. At present, there is no effective treatment for it.
Here, we used different concentrations of GSK-J4 or a combination of GSK-J4 and doxorubicin to treat human Cal-62, 8505C, and 8305C anaplastic thyroid cancer (ATC) cell lines. The experiments were performed using cell viability assays, cell cycle assays, annexin-V/PI binding assays, Transwell migration assays, and wound-healing assays. Tumor xenograft models were used to observe effects .
The half maximal inhibitory concentration (IC50) of GSK-J4 in Cal-62 cells was 1.502 μM, and as the dose of GSK-J4 increased, more ATC cells were blocked in the G2-M and S stage. The combination of GSK-J4 and doxorubicin significantly increased the inhibitory effect on proliferation, especially in KRAS-mutant ATC cells (inhibition rate 38.0%) and (suppresses rate Fa value 0.624, CI value 0.673). The invasion and migration abilities of the KRAS-mutant cell line were inhibited at a low concentration (p < 0.05).
The combination of GSK-J4 with doxorubicin in KRAS-mutant ATC achieved tumor-suppressive effects at a low dose. The synergy of the combination of GSK-J4 and doxorubicin may make it an effective chemotherapy regimen for KRAS-mutant ATC.
间变性甲状腺癌是最具侵袭性的甲状腺癌,预后较差。目前,尚无有效的治疗方法。
在此,我们使用不同浓度的GSK-J4或GSK-J4与阿霉素的组合来处理人Cal-62、8505C和8305C间变性甲状腺癌(ATC)细胞系。实验采用细胞活力测定、细胞周期测定、膜联蛋白-V/PI结合测定、Transwell迁移测定和伤口愈合测定。使用肿瘤异种移植模型观察效果。
GSK-J4在Cal-62细胞中的半数最大抑制浓度(IC50)为1.502μM,随着GSK-J4剂量的增加,更多的ATC细胞被阻滞在G2-M期和S期。GSK-J4与阿霉素的组合显著增强了对增殖的抑制作用,尤其是在KRAS突变的ATC细胞中(抑制率38.0%)以及(抑制率Fa值0.624,CI值0.673)。低浓度时KRAS突变细胞系的侵袭和迁移能力受到抑制(p<0.05)。
GSK-J4与阿霉素联合应用于KRAS突变的ATC时,在低剂量下即实现了肿瘤抑制作用。GSK-J4与阿霉素联合的协同作用可能使其成为KRAS突变的ATC的有效化疗方案。