Background:Bone metastasis of breast cancer (BC) is a key reason for poor prognosis. Recently, natural ingredients derived from plants have been found to exert a broad anti-tumor effect and are considered to be promising candidates for adjuvant therapy. Astragalin (AS) was found to inhibit the progression of several types of tumors; however, the role of AS in regulating the bone metastasis of BC is still unclear.Methods:The effects of AS on the progression of bone metastasis of BC were detected in vivo through safranin O and fast green staining, in vivo living imaging and microCT. The BrdU assay and Annexin V-PI analysis were used to detect the effects of AS on the growth of BC cells. Furthermore, TRAP staining was performed to examine the formation of osteoclasts regulated by AS. A transcriptome was performed to explore the downstream effects of AS on regulating the growth of BC cells, and the mechanism was further confirmed by Western blot and real-time PCR.Results:Administration of AS could effectively attenuate the bone destruction and the progression of bone metastasis of BC. The growth of BC cells can be inhibited by AS by inducing ER stress-mediated upregulation of Ddit3. In addition, AS can also prevent osteoclastogenesis through inhibiting the activation of the AKT pathway.Conclusions:Our studies suggest that AS could be an ideal adjuvant therapy for attenuating the progression of bone metastasis of BC, since it can directly restrict the growth of tumor, as well as attenuate osteolysis.
背景:乳腺癌骨转移是导致预后不良的关键原因。近期研究发现,植物来源的天然成分具有广泛的抗肿瘤作用,被认为是极具潜力的辅助治疗候选药物。研究已证实紫云英苷能够抑制多种肿瘤进展,但其在调控乳腺癌骨转移中的作用机制尚不明确。 方法:通过番红O-固绿染色、活体成像及显微CT技术,在体内检测紫云英苷对乳腺癌骨转移进程的影响。采用BrdU检测与Annexin V-PI分析法评估紫云英苷对乳腺癌细胞增殖的作用。通过TRAP染色观察紫云英苷对破骨细胞形成的调控作用。利用转录组测序技术探究紫云英苷调控乳腺癌细胞生长的下游效应,并通过Western blot和实时荧光定量PCR对相关机制进行验证。 结果:紫云英苷给药能有效减轻骨破坏并抑制乳腺癌骨转移进程。其通过诱导内质网应激介导的Ddit3上调抑制乳腺癌细胞生长。此外,紫云英苷还能通过抑制AKT通路活化来阻止破骨细胞生成。 结论:本研究证实紫云英苷既能直接抑制肿瘤生长,又能减轻骨溶解,可作为抑制乳腺癌骨转移进展的理想辅助治疗策略。
Astragalin Attenuates Bone Destruction and the Progression of Bone Metastasis in Breast Cancer