Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan; Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.
Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan City, Taiwan.
J Surg Res. 2019 Sep;241:8-14. doi: 10.1016/j.jss.2019.03.024. Epub 2019 Apr 17.
Recently, we demonstrated that the expression of 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) in breast cancer is associated with shorter recurrence-free survival, and genetic or pharmacologic inhibition of HSD3B1 reduced colony formation and xenograft growth. However, the mechanisms are unclear.
Triple-negative MDA-MB-231 and BT-20 breast cancer cells underwent HSD3B1 silencing. Microarray and bioinformatic analysis were performed. The interleukin-6 (IL-6) expression and secretion were evaluated using real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Clonogenic ability and cell viability were determined in the absence or presence of recombinant IL-6.
Functional and pathway enrichment analyses showed that HSD3B1 silencing modulates the expression of several growth factors and cytokines. Cells transfected with HSD3B1-targeting small interfering RNA or treated with an HSD3B1 inhibitor (trilostane) had decreased IL-6 expression and secretion. HSD3B1 inhibition reduced colony formation, which was partially rescued by IL-6 supplementation. The HSD3B1 knockdown enhanced paclitaxel sensitivity, and IL-6 treatment partially reversed the augmented cytotoxicity.
Our findings suggest that the therapeutic potential of targeting HSD3B1 is in part mediated by IL-6 suppression.
最近，我们证明了乳腺癌中 3β-羟甾脱氢酶 1 型（HSD3B1）的表达与无复发生存期缩短有关，并且 HSD3B1 的遗传或药物抑制减少了集落形成和异种移植物生长。然而，其机制尚不清楚。
三阴性 MDA-MB-231 和 BT-20 乳腺癌细胞进行了 HSD3B1 沉默。进行了微阵列和生物信息学分析。使用实时定量聚合酶链反应和酶联免疫吸附测定法评估白细胞介素-6（IL-6）的表达和分泌。在不存在或存在重组 IL-6 的情况下测定集落形成能力和细胞活力。
功能和途径富集分析表明，HSD3B1 沉默调节几种生长因子和细胞因子的表达。用 HSD3B1 靶向小干扰 RNA 转染或用 HSD3B1 抑制剂（三氯司坦）处理的细胞中，IL-6 的表达和分泌减少。HSD3B1 抑制减少了集落形成，而 IL-6 补充部分挽救了这一现象。HSD3B1 敲低增强了紫杉醇的敏感性，而 IL-6 处理部分逆转了增强的细胞毒性。
我们的研究结果表明，靶向 HSD3B1 的治疗潜力部分是通过抑制 IL-6 介导的。
