Angiotensin II suppresses adriamycin-induced apoptosis through activation of phosphatidylinositol 3-kinase/Akt signaling in human breast cancer cells.
Angiotensin II (Ang II) stimulates tumor growth and angiogenesis in some solid cancer cells, but its anti-apoptosis role in breast cancer remains unclear. To address this issue, we investigated the effect of Ang II on adriamycin-induced apoptosis in breast cancer MCF-7 cells. Treatment of human breast cancer MCF-7 cells with adriamycin, a DNA topoisomerase II alpha inhibitor, caused apoptosis. However, cells pretreated with Ang II were resistant to this apoptosis. Ang II significantly reduced the ratio of apoptotic cells and stimulation of phospho-Akt-Thr308 and phospho-Akt-Ser473 in a dose-dependent and time-dependent manner. In addition, Ang II significantly prevented apoptosis through inhibiting the cleavage of procaspase-9, a major downstream effector of Akt. The Ang II type 1 receptor (AT1R) was responsible for these effects. Among the signaling molecules downstream of AT1R, we revealed that the phosphatidylinositol 3-kinase/Akt pathway plays a predominant role in the anti-apoptotic effect of Ang II. Our data indicated that Ang II plays a critical anti-apoptotic role in breast cancer cells by a mechanism involving AT1R/phosphatidylinositol 3-kinase/Akt activation and the subsequent suppression of caspase-9 activation.
Zhao
Yanbin
Y
Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin 150040, China.
Chen
Xuesong
X
Cai
Li
L
Yang
Yanmei
Y
Sui
Guangjie
G
Wu
Jin
J
D000804:Angiotensin II / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D000804:Angiotensin II; D004317:Doxorubicin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt