Laboratory of Clinical Biology and Pharmacogenomics and Center for Clinical Research and Genomics, College of Korean Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea.
College of Pharmacy, Gachon University of Medicine and Science, Yeonsu-gu, Incheon, Republic of Korea.
Anticancer Res. 2014 Jun;34(6):2869-82.
This study aimed to examine the effect of apigenin on proliferation and apoptosis in HER2-overexpressing MDA-MB-453 breast cancer cells.
The antiproliferative effects of apigenin were examined by proliferation and MTT assays. The effect of apigenin on apoptotic molecules was determined by western blotting. RT-PCR was performed to measure mRNA levels of HIF-1α and VEGF. ELISA assay was performed to measure intracellular VEGF levels. Immunocytochemistry was performed to evaluate nuclear STAT3 level.
Apigenin inhibited the proliferation of MDA-MB-453 cells. Apigenin up-regulated the levels of cleaved caspase-8 and caspase-3, and induced the cleavage of PARP. Apigenin induced extrinsic apoptosis and blocked the activation (phosphorylation) of JAK2 and STAT3. Apigenin inhibited CoCl2-induced VEGF secretion and decreased the nuclear staining of STAT3.
Apigenin exerts its antiproliferative activity by inhibiting STAT3 signaling. Apigenin could serve as a useful compound to prevent or treat HER2-overexpressing breast cancer.
本研究旨在探讨芹菜素对 HER2 过表达 MDA-MB-453 乳腺癌细胞增殖和凋亡的影响。
通过增殖和 MTT 检测法检测芹菜素的抗增殖作用。通过 Western blot 检测芹菜素对凋亡分子的影响。采用 RT-PCR 检测 HIF-1α 和 VEGF 的 mRNA 水平。通过 ELISA 检测细胞内 VEGF 水平。通过免疫细胞化学检测核 STAT3 水平。
芹菜素抑制 MDA-MB-453 细胞的增殖。芹菜素上调了 cleaved caspase-8 和 caspase-3 的水平，并诱导了 PARP 的切割。芹菜素诱导了细胞外凋亡，并阻断了 JAK2 和 STAT3 的激活（磷酸化）。芹菜素抑制了 CoCl2 诱导的 VEGF 分泌，并减少了 STAT3 的核染色。
芹菜素通过抑制 STAT3 信号通路发挥其抗增殖活性。芹菜素可作为预防或治疗 HER2 过表达乳腺癌的有用化合物。
