组蛋白去乙酰化酶抑制剂对Her2阳性乳腺癌细胞侵袭转移的抑制作用和机制  

Effects and mechanisms of histone deacetylase inhibitors on invasion and metastasis of Her2 positive breast cancer cell

作　　者：尹江[1] 刘浩[1] 郑国沛[1] 谷依学[1] 贺智敏[1] 

机构地区：[1]广州医科大学附属肿瘤医院肿瘤研究所,广州恶性肿瘤治疗转化医学重点实验室,广州510095

出　　处：《中国医师杂志》2017年第2期177-181,共5页Journal of Chinese Physician

基　　金：广州市科技计划项目（201434100061）;广州市卫计委医药卫生科技项目（20161A010090）

摘　　要：目的探讨组蛋白去乙酰化酶抑制剂MS-275和线性肟酸（SAHA）对HER2阳性乳腺癌细胞系BT474和SKBR3侵袭转移能力的影响和可能的作用机制。方法采用4μmol／LMS-275、50μmol／LSAHA分别处理BT474及SKBR3细胞，对照组加入适当体积的PBS，四唑氮化合物（MTS）法检测细胞存活率，流式计数检测细胞凋亡率，Transwell实验检测细胞侵袭转移能力，Western blotting检测相关蛋白表达水平。结果SAHA、MS-275处理的BT474细胞存活率分别为（39±11）％、（54±8）％，SKBR3细胞存活率分别为（62±6）％、（71±9）％；SAHA、MS-275处理BT474细胞的凋亡比例分别为对照组的（8．46±0．29）倍和（4．15±0．71）倍，SKBR3细胞的凋亡比例分别为对照组的（5．51±1．24）倍和（4．04±0．69）倍；BT474细胞对照组、SAHA处理组、MS-275处理组迁移至下室细胞数分别为184．7±18．8、104．3±7．1、131．3±9．1，SKBR3细胞对照组、SAHA处理组、MS-275处理组迁移至下室的细胞数分别为60．0±16．7、14．3±6．5、34．3±8．7；Western结果显示SAHA、MS-275能够抑制BT474、SKBR3细胞中Vimentin、Her2、β-eatenin、HDAC1的表达，上调H3的乙酰化水平及E-eaherin的蛋白表达水平。结论SAHA和MS-275抑制HER2阳性乳腺癌细胞系BT474和SKBR3侵袭转移作用，可能与其抑制Vimentin、Her2、β—catenin，上调E—eaherin表达有关。Objective To investigate the effect of histone deacetylase inhibitor on Her2 positive breast cancer cell line BT474 and SKBR3 in apoptosis and metastasis. Methods Histone deacetylase inhibitor MS-275, suberoylanilide hydroxamic acid （SAHA） （4 μmol/L, and 50 μmol/lL, respectively） treated the cell lines BT474 and SKBR3 cells. Flow eytometer examined the apoptosis ratio. Transwell tested their metastatic activity. Western blot assay was performed to detect the associated proteins. Results SAHA and MS-275 inhibited the cell survival. The BT474 cell survival was （ 39 ± 11 ） %, （ 54 ± 8） %, and the SKBR3 survival was （ 62 ±6 ） % , （ 71 ± 9 ） % , according to the fluorescence-activated cell sorting （FACS） result. SAHA and MS-275 induced the BT474 cell apoptosis 8.46 ±0. 28 （P 〈0. 01 ） ,4. 15 ± 0. 71 （P 〈0. 01 ） fold change, respectively; and upregulated the SKBR3 cell apoptosis ratio 5.51 ± 1.24 （P 〈0. 01 ）, 4. 04 ±0. 69 （P 〈0. 01 ） fold. The Transwell result showed that SAHA, MS-275 inhibited the Transwell ability of BT474 from the control 184. 7 ± 18.8 to 104. 3± 7. 1, 131.3 ±9. 1 per view, and the SKBR3 from control 60 ± 16. 7 per view to 14. 3 ± 6. 5, 34.3 ±8.7 per view . The Western blot result showed that SAHA, MS-275 inhibited the protein level of vimentin, Her2, β-catenin, histone deacetylase inhibitor （ HDACi）, and upregulated the acetylation level of histone 3. The E-caherin protein was regulated in BT474 and SKBR3 cells. Conclusions MS-275, SAHA can induce BT474 and SKBR3 apoptosis significantly, also inhibit their metastatic activity.

关 键 词：组蛋白脱乙酰基酶类/拮抗剂和抑制剂 乳腺肿瘤 肿瘤细胞 培养的 肿瘤侵润 肿瘤转移 

分 类 号：R737.9[医药卫生—肿瘤]