Koduru Srinivas, Sowmyalakshmi Srinivasan, Kumar Raj, Gomathinayagam Rohini, Rohr Jürgen, Damodaran Chendil
Department of Clinical Sciences, College of Health Sciences, University of Kentucky, Lexington, KY 40536, USA.
BMC Cancer. 2009 Jan 30;9:41. doi: 10.1186/1471-2407-9-41.
Breast cancer (BCa)-related mortality still remains the second leading cause of cancer-related deaths worldwide. Patients with BCa have increasingly shown resistance and high toxicity to current chemotherapeutic drugs for which identification of novel targeted therapies are required.
To determine the effect of PDBD on BCa cells, estrogen-receptor positive (ER+)-MCF-7 and estrogen-receptor negative (ER-)-MDA 231 cells were treated with PDBD and the cell viability, apoptotic, cell cycle, Western blot and Promoter assays were performed.
PDBD inhibits cell viability of ER+ and ER- BCa cells by inducing apoptosis without causing significant toxicity in normal breast epithelial cells. While dissecting the mechanism of action of PDBD on BCa, we found that PDBD inhibits Akt signaling and its downstream targets such as NF-kappaB activation, IAP proteins and Bcl-2 expression. On the other hand, activation of JNK/p38 MAPK-mediated pro-apoptotic signaling was observed in both ER+ and ER- BCa cells.
These findings suggest that PDBD may have wide therapeutic application in the treatment of BCa.
乳腺癌（BCa）相关死亡率仍是全球癌症相关死亡的第二大主要原因。BCa患者对当前化疗药物的耐药性日益增加且毒性较大，因此需要鉴定新的靶向治疗方法。
为了确定PDBD对BCa细胞的作用，用PDBD处理雌激素受体阳性（ER+）-MCF-7细胞和雌激素受体阴性（ER-）-MDA 231细胞，并进行细胞活力、凋亡、细胞周期、蛋白质免疫印迹和启动子分析。
PDBD通过诱导凋亡抑制ER+和ER-BCa细胞的活力，且对正常乳腺上皮细胞无明显毒性。在剖析PDBD对BCa的作用机制时，我们发现PDBD抑制Akt信号及其下游靶点，如NF-κB激活、IAP蛋白和Bcl-2表达。另一方面，在ER+和ER-BCa细胞中均观察到JNK/p38 MAPK介导的促凋亡信号激活。
这些发现表明PDBD在BCa治疗中可能具有广泛的治疗应用。
