| Yanping Gao,Zhiyong Dong,Jun Bai. A novel derivative of Genistein inhibits proliferation of ovarian cancer HO-8910 cells by regulating reactive oxygen species. Oncol Transl Med, 2022, 8: 285-292. |
| 新型金雀异黄素衍生物调节活性氧表达抑制卵巢HO-8910细胞增殖 |
| A novel derivative of Genistein inhibits proliferation of ovarian cancer HO-8910 cells by regulating reactive oxygen species |
| Received:September 10, 2022 Revised:December 29, 2022 |
| DOI：10.1007/s10330-022-0596-6 |
| 中文关键词: 卵巢癌；5-羟基-4 |
| 英文关键词: ovarian cancer; 5-hydroxy-4’-nitro-7-propionyloxy-genistein; reactive oxygen species; proliferation; apoptosis |
| 基金项目: |
| Author Name | Affiliation | E-mail | | Yanping Gao | The First People''s Hospital of Datong | gaoyanpingdtu@163.com | | Zhiyong Dong | The First Affiliated Hospital of Jinan University | | | Jun Bai* | The First People''s Hospital of Datong | baijunjinanu@163.com |
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| 中文摘要: |
| 摘要：目的 检测金雀异黄素新型衍生物5-羟基-4"-硝基-7-丙酰氧基金雀异黄素（5-hydroxy- 4"-nitro-7-propionyloxy- genistein, HNPG）对卵巢癌HO-8910细胞增殖的抑制作用及其可能分子生物学机制。方法 体外培养卵巢癌HO-8910细胞，用MTT法检测HNPG对MG-63细胞的增殖抑制作用；用AV-PI染色FCM检测HNPG对HO-8910细胞的凋亡诱导作用；用DCFH-DA染色FCM检测HNPG对HO-8910细胞活性氧的影响；用Rh 123染色FCM检测HNPG对HO-8910细胞的膜电位影响；用ELISA检测HNPG对HO-8910细胞的SOD、CAT、GSH和MDA影响；用Western blotting检测 HNPG对HO-8910细胞bcl-2、bax、cyt-c和cleaved-caspase-3蛋白表达的影响。结果 HNPG在体外呈时间和浓度依赖性抑制HO-8910细胞增殖并诱导凋亡，同时SOD和CAT生物活性下调，GSH含量下降，MDA含量上升，ROS表达上调，线粒体膜电位表达降低，与NS组比较组间有统计学意义（P＜0.05）；伴随着bax、cyt-c和cleaved-caspase-3蛋白表达上调，bcl-2蛋白表达降低，与NS组比较组间有统计学意义（P＜0.05）。结论 HNPG在体外可以显著抑制HO-8910细胞增殖，其机制可能与其调节细胞内SOD、CAT和GSH表达，上调活性氧含量，损伤线粒体内膜，诱导细胞线粒体途径凋亡。 |
| 英文摘要: |
| Objective To investigate the anticancer effect of a novel derivative of genistein (5-hydroxy-4’-nitro-7-
propionyloxy-genistein, HNPG) on human ovarian cancer HO-8910 cells and its possible molecular
mechanism.
Methods HO-8910 cells were cultured in vitro, and the inhibitory effect of HNPG on proliferation was
determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The effect of
HNPG on inducing apoptosis was examined using FCM with Annexin V-FITC and propidium iodide staining.
The effect of HNPG on regulating reactive oxygen species (ROS) was measured using FCM with 2’,7’?di
chlorodihydro?fluorescein diacetate staining. The effect of HNPG on modulating mitochondrial membrane
potential (MMP) was determined using FCM with lipophilic cationic dye 2 (6 Amino 3 imino 3H xanthen 9
yl) benzoic acid methyl ester (Rh123) staining. The bioactivity of superoxide dismutase (SOD) and catalase
(CAT) and the content of glutathione (GSH) and malondialdehyde (MDA) were detected using enzymelinked
immunosorbent assay. The related apoptotic proteins, including bcl-2, bax, cyt-c, and cleavedcaspase-
3, were assessed using western blotting.
Results HNPG exhibited dramatic antitumor activity against HO-8910 cells in vitro, inhibited proliferation,
and induced apoptosis in a time- and dose-dependent manner. These effects were accompanied by reduced
bioactivity of SOD and CAT, reduced GSH content, and enhanced MDA content. Simultaneously, the
amount of ROS was increased and the level of MMP was reduced, along with upregulation of mitochondrial
apoptosis pathway-related proteins, bax, cyt-c, and cleaved-caspase-3; bcl-2 protein was downregulated.
Conclusion HNPG inhibited proliferation of human ovarian cancer HO-8910 cells in vitro, which might
be related to decreased bioactivity of SOD and CAT. HNPG also reduced GSH content, which resulted in
ROS accumulation in cells, damaged the integrity of mitochondrial membrane, and induced cell apoptosis |
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