Department of Biochemistry, School of Medicine, China Medical University, Taichung, Taiwan.
Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan.
Taiwan J Obstet Gynecol. 2021 Mar;60(2):266-272. doi: 10.1016/j.tjog.2021.01.002.
Ovarian cancer is the most lethal of the gynecologic malignancies. Most women have advanced disease at diagnosis and require extensive debulking surgery and aggressive chemotherapy. Induction of apoptosis in cancer cells has been used as an important approach for cancer therapy. We examined the anticancer effect of 6,7-methylenedioxy-4-(2,4-dimethoxyphenyl)quinolin-2(1H)-one (12e) in human ovarian cancer cell line.
The 6,7-methylenedioxy-4- (2,4-dimethoxyphenyl) quinolin-2 (1H) -one (12e) was synthesized and provided by Dr. Li-Jiau Huang of China Medical University. Cell viability analysis showed that 12e inhibited cell growth and induced cell death in time- and dose-dependent manners. In order to study the underlying cell death mechanism, 2774 and SKOV3 cells treated with 12e were studied by morphology, DAPI/TUNEL double staining, DNA gel electrophoresis. To search the mechanisms of anti-proliferative effect of 12e, cell cycle analysis was performed. Changes in proteins related to cell death were analyzed by Western blot.
12e significantly induced apoptosis evidenced by morphological changes, TUNEL-DAPI double-staining and DNA fragmentation. Western blot analysis demonstrated that the protein level of Bcl-2 was decreased after treatment with 12e, while the level of p53 and Bax was increased. 12e treatment resulted in G2/M arrest through down modulation of cyclin B1 and cdk1.
These results suggested that 12e -induced growth inhibition was associated with cell cycle arrest and apoptosis.
卵巢癌是妇科恶性肿瘤中最致命的一种。大多数女性在诊断时已处于晚期疾病状态，需要进行广泛的肿瘤细胞减灭术和强化化疗。诱导癌细胞凋亡已被用作癌症治疗的重要方法。我们研究了 6,7-亚甲二氧基-4-(2,4-二甲氧基苯基)喹啉-2(1H)-酮（12e）在人卵巢癌细胞系中的抗癌作用。
6,7-亚甲二氧基-4-(2,4-二甲氧基苯基)喹啉-2(1H)-酮（12e）由中国医科大学的黄丽昭博士合成并提供。细胞活力分析表明，12e 以时间和剂量依赖的方式抑制细胞生长并诱导细胞死亡。为了研究潜在的细胞死亡机制，用 12e 处理 2774 和 SKOV3 细胞，并通过形态学、DAPI/TUNEL 双重染色、DNA 凝胶电泳进行研究。为了研究 12e 抗增殖作用的机制，进行了细胞周期分析。通过 Western blot 分析了与细胞死亡相关的蛋白质变化。
12e 显著诱导细胞凋亡，表现为形态学变化、TUNEL-DAPI 双重染色和 DNA 片段化。Western blot 分析表明，用 12e 处理后 Bcl-2 蛋白水平降低，而 p53 和 Bax 水平升高。12e 通过下调细胞周期蛋白 B1 和 CDK1 导致 G2/M 期阻滞。
这些结果表明，12e 诱导的生长抑制与细胞周期阻滞和凋亡有关。
