Wang Xiaoxiong, Chen Shirong, Shen Taipeng, Lu Hao, Xiao Dingqiong, Zhao Meng, Yao Yutang, Li Xiuli, Zhang Ge, Zhou Xing, Jiang Xiao, Cheng Zhuzhong
Positron Emission Tomography/Computed Tomography Center, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610041, P.R. China.
Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, Sichuan 610041, P.R. China.
Exp Ther Med. 2020 Mar;19(3):1687-1694. doi: 10.3892/etm.2020.8422. Epub 2020 Jan 3.
Breast cancer remains one of the leading causes of mortality in women, and epithelial-mesenchymal transition (EMT) serves an indispensable role in the invasion and migration of breast cancer cells. As a representative of classical histone deacetylase inhibitors (HDACIs), trichostatin A (TSA) has been demonstrated to reverse EMT in certain types of non-tumor cells and tumor cells. In the present study, the invasive and migratory abilities of MCF-7 cells were examined following treatment with TSA. TSA-induced changes in the expression of an epithelial biomarker epithelial cadherin (E-cadherin), a mesenchymal biomarker (vimentin), and a transcription factor [zinc finger protein SNAI2 (SLUG)] were also investigated. Transwell invasion and migration assays, and wound healing assays, revealed that the invasive and migratory abilities of MCF-7 cells were suppressed significantly upon treatment with TSA. Treatment with TSA led to an increased expression level of E-cadherin, and decreased expression of vimentin and, in MCF-7 cells. The overexpression of SLUG decreased the expression level of E-cadherin, but increased vimentin expression, and upon treatment with TSA, these effects were reversed. Additionally, SLUG knockdown also led to upregulation of E-cadherin expression, downregulation of vimentin expression, and suppression of the invasion and migration of MCF-7 cells. Taken together, these results suggest that TSA is able to reverse EMT via suppressing SLUG and attenuate the invasion and migration of MCF-7 cells , thereby providing a potential avenue for chemotherapeutic intervention in the treatment of breast cancer.
乳腺癌仍然是女性死亡的主要原因之一，上皮-间质转化（EMT）在乳腺癌细胞的侵袭和迁移中起着不可或缺的作用。作为经典组蛋白去乙酰化酶抑制剂（HDACIs）的代表，曲古抑菌素A（TSA）已被证明能使某些类型的非肿瘤细胞和肿瘤细胞发生EMT逆转。在本研究中，检测了TSA处理后MCF-7细胞的侵袭和迁移能力。还研究了TSA诱导的上皮生物标志物上皮钙黏蛋白（E-钙黏蛋白）、间质生物标志物（波形蛋白）和转录因子[锌指蛋白SNAI2（SLUG）]表达的变化。Transwell侵袭和迁移试验以及伤口愈合试验表明，TSA处理后MCF-7细胞的侵袭和迁移能力显著受到抑制。TSA处理导致MCF-7细胞中E-钙黏蛋白表达水平升高，波形蛋白表达降低。SLUG的过表达降低了E-钙黏蛋白的表达水平，但增加了波形蛋白的表达，而TSA处理后，这些作用被逆转。此外，SLUG基因敲低也导致E-钙黏蛋白表达上调、波形蛋白表达下调，并抑制了MCF-7细胞的侵袭和迁移。综上所述，这些结果表明TSA能够通过抑制SLUG逆转EMT，并减弱MCF-7细胞的侵袭和迁移，从而为乳腺癌治疗的化疗干预提供了一条潜在途径。
