Wang Diyu, Yin Lei, Wei Jinrong, Yang Zhixue, Jiang Guoqin
1 Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
2 Department of General Surgery, Suzhou Wuzhong People's Hospital, Suzhou, China.
Tumour Biol. 2017 Apr;39(4):1010428317698338. doi: 10.1177/1010428317698338.
Breast cancer is a malignant tumor that is harmful to women's health around the world. Investigating the biological mechanism is, therefore, of pivotal importance to improve patients' prognoses. Compared to non-neoplastic tissues, enhanced glucose and lipid metabolism is one of the most common properties of malignant breast cancer. Adenosine triphosphate (ATP) citrate lyase is a key enzyme linking aerobic glycolysis and fatty acid synthesis and is of high biological and prognostic significance in breast cancer. In our clinical study, fresh clinical tissues were used to analyze ATP citrate lyase expression by western blotting, and paraffin archived samples from 62 breast cancer patients were used to analyze ATP citrate lyase expression by immunohistochemistry. In the cellular study, following small interfering RNA-mediated inhibition of ATP citrate lyase in MCF-7 cells, cell viability and apoptosis were measured using the Cell Counting Kit-8 and flow cytometry, respectively. Breast cancer tissues showed strong expression of ATP citrate lyase, whereas adjacent normal tissues showed weak expression. Silencing of endogenous ATP citrate lyase expression by small interfering RNA in MCF-7 cells suppressed cell viability and increased cell apoptosis. Collectively, our study revealed that expression of ATP citrate lyase was significantly increased in breast cancer tissue compared with normal tissue. In addition, we found that depletion of ATP citrate lyase suppressed tumor growth, which suggests that ATP citrate lyase-related inhibitors might be potential therapeutic approaches for breast cancer.
乳腺癌是一种对全球女性健康有害的恶性肿瘤。因此，研究其生物学机制对于改善患者预后至关重要。与非肿瘤组织相比，葡萄糖和脂质代谢增强是恶性乳腺癌最常见的特征之一。三磷酸腺苷（ATP）柠檬酸裂解酶是连接有氧糖酵解和脂肪酸合成的关键酶，在乳腺癌中具有很高的生物学和预后意义。在我们的临床研究中，使用新鲜临床组织通过蛋白质印迹法分析ATP柠檬酸裂解酶的表达，并使用来自62例乳腺癌患者的石蜡存档样本通过免疫组织化学分析ATP柠檬酸裂解酶的表达。在细胞研究中，在MCF-7细胞中通过小干扰RNA介导抑制ATP柠檬酸裂解酶后，分别使用细胞计数试剂盒-8和流式细胞术测量细胞活力和细胞凋亡。乳腺癌组织中ATP柠檬酸裂解酶表达强烈，而相邻正常组织中表达较弱。在MCF-7细胞中通过小干扰RNA沉默内源性ATP柠檬酸裂解酶表达可抑制细胞活力并增加细胞凋亡。总体而言，我们的研究表明，与正常组织相比，乳腺癌组织中ATP柠檬酸裂解酶的表达显著增加。此外，我们发现ATP柠檬酸裂解酶的缺失会抑制肿瘤生长，这表明与ATP柠檬酸裂解酶相关的抑制剂可能是乳腺癌潜在的治疗方法。
