Li Zhilan, Jiang Xiudi, Chen Peihong, Wu Xuebing, Duan Aihua, Qin Yiyu
Department of Clinical Laboratory, The Seventh People's Hospital of Shanghai, Shanghai 200137, P.R. China.
Department of Blood Transfusion, The Seventh People's Hospital of Shanghai, Shanghai 200137, P.R. China.
Oncol Lett. 2018 Sep;16(3):4033-4042. doi: 10.3892/ol.2018.9105. Epub 2018 Jul 10.
Anaplastic thyroid cancer (ATC) represents the most aggressive subtype of thyroid cancer and has a poor prognosis. In addition to surgery, chemotherapy is an important treatment for ATC; however, the therapeutic effects of current chemotherapies for ATC are not particularly promising. There is a high proportion of side population (SP) cells in ATC, which may be a reason for its drug resistance. In the present study, the antitumor activities of combined octreotide (OCT) and cisplatin (DDP) on the proliferation and apoptosis of ATC SP cells were evaluated. First, SP cells from 8305C and BHT101 cell lines were detected and sorted. Following culture for 1 week, cluster of differentiation (CD)44, CD133, ATP-binding cassette (ABC) subfamily B member 1 (ABCB1), ABC subfamily G member 2 (ABCG2) and somatostatin receptor expression was detected to characterize the SP cells. An MTT assay was performed to investigate the combined effects on 8305C-SP cell proliferation , and a mouse model was used to investigate the combined effects on 8305C-SP cell proliferation . Annexin V/propidium iodide staining was used to investigate the combined effects on 8305C-SP cell apoptosis. Chemotherapeutic drug resistance-associated protein expression and apoptosis-associated protein expression were also detected following combined treatment. As a result, SP cells were identified in 8305C and BHT101 cells, and the proportion of 8305C-SP cells was increased compared with that of BTH101-SP cells. SP cells have enhanced proliferation, tumorigenicity and drug resistance compared with main population cells. The combined treatment of OCT with DDP suppressed the proliferation of 8305C-SP cells and , and induced 8305C-SP cell apoptosis. Combined treatment decreased the ABCB1 and ABCG2 expression by SP cells and activated mitochondrial apoptotic signaling, resulting in cell apoptosis. In conclusion, these data support the hypothesis that combined treatment with OCT and DDP induces ATC cell apoptosis and suppresses cell proliferation. These data provide a theoretical basis for further combined chemotherapy clinical applications.
间变性甲状腺癌（ATC）是甲状腺癌中侵袭性最强的亚型，预后较差。除手术外，化疗是ATC的重要治疗方法；然而，目前用于ATC的化疗疗效并不特别理想。ATC中存在高比例的侧群（SP）细胞，这可能是其耐药的原因之一。在本研究中，评估了奥曲肽（OCT）和顺铂（DDP）联合应用对ATC SP细胞增殖和凋亡的抗肿瘤活性。首先，检测并分选了来自8305C和BHT101细胞系的SP细胞。培养1周后，检测分化簇（CD）44、CD133、ATP结合盒（ABC）亚家族B成员1（ABCB1）、ABC亚家族G成员2（ABCG2）和生长抑素受体表达，以对SP细胞进行表征。进行MTT试验以研究对8305C-SP细胞增殖的联合作用，并使用小鼠模型研究对8305C-SP细胞增殖的联合作用。采用膜联蛋白V/碘化丙啶染色法研究对8305C-SP细胞凋亡的联合作用。联合治疗后还检测了化疗耐药相关蛋白表达和凋亡相关蛋白表达。结果，在8305C和BHT101细胞中鉴定出SP细胞，与BTH101-SP细胞相比，8305C-SP细胞的比例增加。与主要群体细胞相比，SP细胞具有更强的增殖、致瘤性和耐药性。OCT与DDP联合治疗抑制了8305C-SP细胞的增殖，并诱导了8305C-SP细胞凋亡。联合治疗降低了SP细胞中ABCB1和ABCG2的表达，并激活了线粒体凋亡信号，导致细胞凋亡。总之，这些数据支持OCT和DDP联合治疗诱导ATC细胞凋亡并抑制细胞增殖这一假说。这些数据为进一步的联合化疗临床应用提供了理论依据。
