Zhou Le, Zhang Mengchao, Fu Qingfeng, Li Jingting, Sun Hui
Department of Thyroid Surgery, China-Japan Union Hospital, Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Changchun 130033, China.
Radiology Department, China-Japan Union Hospital, Jilin University, Changchun 130033, China.
Oncotarget. 2016 Feb 9;7(6):6878-90. doi: 10.18632/oncotarget.6901.
Treatment of thyroid cancer has incurred much focus because of its high prevalency. As a new strategy treating thyroid cancer, hyperthermia takes several advantages compared with surgery or chemotherapy, including minimal invasion, low systematic toxicity and the ability to enhance the immunogenicity of cancer cells with the expression Hsp70 which serves as Toll-like receptors-4 (TLR-4 agonist). However, Hsp70 as a molecular chaperone can protect cells from heat induced apoptosis and therefore compromise the tumor killing effect of hyperthermia. In this study, to solve this problem, a combined hyperthermia therapy was employed to treat thyroid cancer. We prepared a probe with the tumor targeting agent AG to monitor thyroid tumor issue and generate heat to kill tumor cells in vivo. At the same time Quercetin (inhibitor of HSP70) and lipopolysaccharide (LPS) (agonist of TLR-4) were used for the combined hyperthermia therapy. The results showed that compared with free IR820, AG modification facilitated much enhanced cellular uptake and greatly pronounced tumor targeting ability. The combined therapy exhibited the most remarkable tumor inhibition compared with the single treatments both in vitro and in vivo. These findings verified that the new therapeutic combination could significantly improve the effect of hyperthermia and shed light on a novel clinical strategy in thyroid cancer treatment.
甲状腺癌因其高发病率而备受关注。作为一种治疗甲状腺癌的新策略，热疗与手术或化疗相比具有诸多优势，包括微创、低全身毒性以及能够通过作为Toll样受体4（TLR - 4激动剂）的热休克蛋白70（Hsp70）的表达来增强癌细胞的免疫原性。然而，Hsp70作为一种分子伴侣可以保护细胞免受热诱导的凋亡，从而削弱热疗的肿瘤杀伤效果。在本研究中，为了解决这个问题，采用了联合热疗来治疗甲状腺癌。我们制备了一种带有肿瘤靶向剂AG的探针，用于监测甲状腺肿瘤组织并在体内产热以杀死肿瘤细胞。同时，使用槲皮素（HSP70抑制剂）和脂多糖（LPS）（TLR - 4激动剂）进行联合热疗。结果表明，与游离的IR820相比，AG修饰促进了细胞摄取的显著增强和肿瘤靶向能力的大大提高。与单一治疗相比，联合治疗在体外和体内均表现出最显著的肿瘤抑制作用。这些发现证实了这种新的治疗组合可以显著提高热疗效果，并为甲状腺癌治疗的新临床策略提供了思路。
