Department of Physiology, Qiqihar Medical College, Qiqihar, 161006, PR China; Department of Research Section of Integrated Traditional Chinese and Western Medicine, Heilongjiang University of Chinese Medicine, Harbin, 150040, PR China.
Grade 2019 of Acupuncture and Massage, Heilongjiang University of Chinese Medicine, Harbin, 150040, PR China.
J Ethnopharmacol. 2022 Jan 10;282:114581. doi: 10.1016/j.jep.2021.114581. Epub 2021 Aug 28.
The diterpenoids extracted from Euphorbia kansui S.L. Liou ex S.B.Ho, Euphorbia fischeriana Steud. have good antitumor effects. Jolkinolide B has anti-breast cancer effect, but it is unclear whether it has different therapeutic effects between luminal A subtype and luminal B subtype breast cancer.
This study investigated the Jolkinolide B has different therapeutic, important targets and pathways effects between luminal A subtype and luminal B subtype breast cancer.
We used bioinformatics to predict the biological process and molecular mechanism of Jolkinolide B in treating two types of breast cancer. Then, in vitro, cultured MCF-7 cells and BT-474 cells were divided into control group, PI3K inhibitor + control group, Jolkinolide B group and PI3K inhibitor + Jolkinolide B group. The CCK-8 assay, Flow cytometric analysis and Transwell cell migration assay was used to detect the cell proliferation, apoptosis, and migration in each group, respectively. ELISA was used to measure the content of Akt and phosphorylated Akt (p-Akt) in cell lysis buffer.
Compared to luminal A breast cancer, Jolkinolide B had more targets, proliferation, migration processes and KEGG pathways when treating luminal B subtype breast cancer. Jolkinolide B significantly prolonged the survival time of luminal B subtype breast cancer patients. Compared to the control group, the cell proliferation absorbance value (A value) and migration number of the two kinds of breast cancer cells in the Jolkinolide B group were decreased (P < 0.01, n = 6), and the number of apoptotic cells was increased (P < 0.01, n = 6). Compared to the Jolkinolide B group, the A value and migration number of the two types of breast cancer cells were significantly decreased in the PI3K inhibitor + Jolkinolide B group (P < 0.01, n = 6), and the number of apoptotic cells was significantly increased (P < 0.01, n = 6). In addition, compared to MCF-7 cells, the A value and migration number of BT-474 cells stimulated with Jolkinolide B were significantly decreased (P < 0.01, n = 6), and the number of apoptotic cells was significantly increased (P < 0.01, n = 6). Akt and p-Akt protein levels in the two breast cancer cell lines in the Jolkinolide B group were all decreased (P < 0.01, n = 6), especially in BT-474 cells stimulated by Jolkinolide B.
Jolkinolide B regulates the luminal A and luminal B subtypes of breast cancer through PI3K-Akt, EGFR and other pathways. Jolkinolide B has more significant therapeutic effect on luminal B subtype breast cancer. In vitro, experiments verified that Jolkinolide B significantly inhibited the proliferation and migration activity of BT-474 breast cancer cells by downregulating the PI3K-Akt pathway.
从甘遂 Euphorbia kansui S.L. Liou ex S.B.Ho 和密毛甘遂 Euphorbia fischeriana Steud. 中提取的二萜类化合物具有良好的抗肿瘤作用。乔利酮 B 具有抗乳腺癌作用，但尚不清楚它在腔 A 型和腔 B 型乳腺癌亚型之间是否具有不同的治疗效果。
本研究旨在探讨乔利酮 B 在治疗两种乳腺癌亚型中的不同治疗靶点和途径的作用。
我们使用生物信息学方法预测了乔利酮 B 治疗两种乳腺癌的生物学过程和分子机制。然后，在体外培养 MCF-7 细胞和 BT-474 细胞，分为对照组、PI3K 抑制剂+对照组、乔利酮 B 组和 PI3K 抑制剂+乔利酮 B 组。用 CCK-8 测定法、流式细胞术分析和 Transwell 细胞迁移试验分别检测各组细胞的增殖、凋亡和迁移情况。用 ELISA 法测定细胞裂解缓冲液中 Akt 和磷酸化 Akt（p-Akt）的含量。
与腔 A 型乳腺癌相比，乔利酮 B 在治疗腔 B 型乳腺癌时具有更多的靶点、增殖和迁移过程以及 KEGG 途径。乔利酮 B 显著延长了腔 B 型乳腺癌患者的生存时间。与对照组相比，两种乳腺癌细胞在乔利酮 B 组中的细胞增殖吸光度值（A 值）和迁移数量均降低（P<0.01，n=6），凋亡细胞数量增加（P<0.01，n=6）。与乔利酮 B 组相比，PI3K 抑制剂+乔利酮 B 组两种乳腺癌细胞的 A 值和迁移数量明显降低（P<0.01，n=6），凋亡细胞数量明显增加（P<0.01，n=6）。此外，与 MCF-7 细胞相比，BT-474 细胞在乔利酮 B 刺激下的 A 值和迁移数量明显降低（P<0.01，n=6），凋亡细胞数量明显增加（P<0.01，n=6）。乔利酮 B 组两种乳腺癌细胞系中的 Akt 和 p-Akt 蛋白水平均降低（P<0.01，n=6），尤其是在 BT-474 细胞中。
乔利酮 B 通过 PI3K-Akt、EGFR 等途径调节腔 A 型和腔 B 型乳腺癌。乔利酮 B 对腔 B 型乳腺癌亚型的治疗效果更为显著。体外实验验证了乔利酮 B 通过下调 PI3K-Akt 通路显著抑制 BT-474 乳腺癌细胞的增殖和迁移活性。
