过表达Bcl-2引起的凋亡耐受是形成耐药的机制之一,近来发现Bcl-2具有调节细胞代谢与凋亡的双重作用。我们的实验发现Bcl-2抑制剂S1能够引起细胞糖酵解相关基因表达下调，而糖酵解抑制剂能够提高S1诱导的细胞凋亡敏感性。提示抑制Bcl-2诱导细胞凋亡与代谢重编程有关。我们还发现卵巢癌耐药细胞高表达Bcl-2，低表达线粒体去乙酰化酶SIRT3。作为线粒体蛋白乙酰化调节的主要因子，去乙酰化酶SIRT3活性依赖NAD+，参与了线粒体相关代谢途径的调节。因此，我们推测抑制Bcl-2可能改变癌细胞代谢，活化SIRT3，SIRT3通过细胞糖酵解及线粒体氧化磷酸化途径调控了细胞凋亡。为了验证这一假设，我们观察抑制Bcl-2诱导卵巢癌耐药细胞凋亡时，糖代谢表型的改变。检测SIRT3对代谢重编程及凋亡敏感性的影响，分析SIRT3与Bcl-2整合细胞代谢与凋亡的机制，为克服肿瘤耐药提供新的思路。

Overexpression of the anti-apoptosis protein Bcl-2 was involved in drug resistance.Recent studies imply that Bcl-2 plays a dual role in the regulation of metabolic reprogramming and apoptosis.Our previous studies have found that the Bcl-2 inhibitor S1 was able to down-regulate the transcriptional level of glycolysis related genes, while inhibition of glycolysis could sensitize cells to the apoptosis induced by S1. These suggested that the role of Bcl-2 involved in apoptosis resistance may intertwine with its role participating in cancer cell metabolism reprogramming. Besides, there was a negative correlation between the expression level of protein Bcl-2 and SIRT3 in drug-resistant ovarian cancer cells. As a key regulator of Mitochondrial Protein Acetylation, NAD-dependent deacetylase SIRT3 regulates the mitochondria related metabolic pathways.Therefore, we initially speculated that inhibition of Bcl-2 may activate SIRT3 through altering the cell metabolism, while SIRT3 may regulate apoptosis through affecting glycolysis and mitochondrial oxidative phosphorylation pathway. To test this hypothesis, we observe the changes of glucose metabolism pattern in ovarian cancer cells through inhibiting Bcl-2,study the effects of SIRT3 on the metabolic reprogramming and apoptosis, and analyze the mechanisms involved in the integration of cell metabolism and apoptosis through SIRT3 and Bcl-2, providing a new way to overcome tumor drug resistance.