Department of Histology, Faculty of Medicine, Udayana University, Bali, Indonesia.
Department of Anatomical Pathology, Faculty of Medicine, Udayana University, Bali, Indonesia.
Asian Pac J Cancer Prev. 2020 May 1;21(5):1213-1219. doi: 10.31557/APJCP.2020.21.5.1213.
Most of breast cancer patients are estrogen receptor alpha-positive and have high resistance and side effect of chemotherapeutic drug. Therefore, discovering an effective anticancer agent is needed. This research explored the effect of (E)-1-(4'-aminophenyl)-3-phenylprop-2-en-1-one (APE) on miR-18a, Dicer1, and MMP-9 expressions.
Twenty four female Sprague-Dawley rats were invetigated in this study. The rats were divided into 6 groups of 4. G1 was considered as normal rat. G2, G3, T1, T2, and T3 were given DMBA 20 mg/kgBW twice a week for 5 weeks to induce mammary cancer. After being affiliated with cancer, G2 was given vehicle and G3 was treated with tamoxifen. T1, T2, and T3 were treated with APE intraperitoneally everyday for 21 days at doses of 5, 15, and 45 mg/kgBW/day, respectively. Blood plasma was collected to measure miR-18a expression using qRT-PCR. Mammary tissues were also collected to determine Dicer1 and MMP-9 expressions by using immunohistochemistry.
The results showed significant down-regulation of miR-18a relative expression and up-regulation of Dicer1 expression in G3 and T1 compared to G2 (P<0.05). MMP-9 expression has significant decrease in T1 compared to G2 (P<0.05).
APE can decrease miR-18a and MMP-9 expressions and increase Dicer1 expression in rat mammary cancer. Therefore, this compound could be a candidate of novel anticancer.
大多数乳腺癌患者雌激素受体α阳性，对化疗药物有高耐药性和副作用。因此，需要发现一种有效的抗癌药物。本研究探讨了（E）-1-（4'-氨基苯基）-3-苯基-2-丙烯-1-酮（APE）对 miR-18a、Dicer1 和 MMP-9 表达的影响。
本研究共纳入 24 只雌性 Sprague-Dawley 大鼠。将大鼠分为 6 组，每组 4 只。G1 为正常大鼠。G2、G3、T1、T2 和 T3 每周两次给予 DMBA 20mg/kgBW，共 5 周，诱导乳腺癌。患癌后，G2 给予载体，G3 给予他莫昔芬治疗。T1、T2 和 T3 分别给予 APE 腹腔注射，剂量为 5、15 和 45mg/kgBW/天，共 21 天。采集血血浆，采用 qRT-PCR 检测 miR-18a 表达。收集乳腺组织，采用免疫组织化学法检测 Dicer1 和 MMP-9 表达。
结果显示，与 G2 相比，G3 和 T1 组 miR-18a 相对表达量显著下调，Dicer1 表达显著上调（P<0.05）。与 G2 相比，T1 组 MMP-9 表达显著下降（P<0.05）。
APE 可降低大鼠乳腺癌中 miR-18a 和 MMP-9 的表达，增加 Dicer1 的表达。因此，该化合物可能是一种新型抗癌药物的候选药物。
