Zhang Yan, Sheng Zhizhong, Su Chi, Xia Yuli, Chen Xiangfan, Huang Xiaobo, Li Honglin, Ma Changsheng, Wang Ligang
Pediatric Orthopedics, Shenzhen Pingle Orthopedic Hospital, No. 30, Dongyuan Road, Futian District, Shenzhen City 518000, Guangdong Province, China.
Evid Based Complement Alternat Med. 2022 Dec 23;2022:4026688. doi: 10.1155/2022/4026688. eCollection 2022.
Caudatin is a steroidal glycoside with reported anticancer activity in a variety of studies. Nevertheless, the role and mechanisms of caudatin in osteosarcoma (OS) remain unclear. In this study, we explored the potential anticancer effects of caudatin in OS cells and investigated the underlying mechanisms.
Both the CCK8 proliferation assay and flow cytometry were employed to evaluate cell proliferation and apoptosis. A transwell assay was applied to determine cell invasion ability. Besides, glycolytic capacity was examined by measuring glucose consumption, lactic acid production, as well as ATP production. A western blot was utilized to assess the protein levels of -catenin, CyclinD 1, C-myc, HK2 (Hexokinase 2), LDHA (lactate dehydrogenase), as well as epithelial-mesenchymal transition (EMT)-related markers. The inhibitory effect of caudatin on tumor growth was investigated using a xenograft tumorigenesis model.
Caudatin restrained cellular glycolysis, suppressed cell proliferation and invasion by reducing HK2 and LDHA expression and regulating the Wnt/-Catenin signaling pathway. Caudatin treatment caused the upregulation of E-cadherin and suppressed N-cadherin expression. Further, caudatin treatment impaired cell viability, invasion ability, and intracellular glycolysis level but induced apoptosis. The administration of BML 284 reversed the inhibitory effects of caudatin. Moreover, caudatin suppressed the tumorigenesis of OS cells in the xenograft model of nude mice.
Our study revealed the anticancer effects of caudatin, including proliferation inhibition, cell invasion suppression, and glycolysis impairment. These effects seem to be executed through targeting the Wnt/-Catenin signaling pathway. These data indicate that caudatin may be formulated as a potential therapeutic for osteosarcoma.
在多项研究中，牛膝甾酮是一种具有抗癌活性的甾体糖苷。然而，牛膝甾酮在骨肉瘤（OS）中的作用和机制仍不清楚。在本研究中，我们探讨了牛膝甾酮对OS细胞的潜在抗癌作用，并研究了其潜在机制。
采用CCK8增殖试验和流式细胞术评估细胞增殖和凋亡。应用Transwell试验测定细胞侵袭能力。此外，通过测量葡萄糖消耗、乳酸产生以及ATP产生来检测糖酵解能力。利用蛋白质免疫印迹法评估β-连环蛋白、细胞周期蛋白D1、C-myc、己糖激酶2（HK2）、乳酸脱氢酶A（LDHA）以及上皮-间质转化（EMT）相关标志物的蛋白质水平。使用异种移植瘤模型研究牛膝甾酮对肿瘤生长的抑制作用。
牛膝甾酮通过降低HK2和LDHA表达并调节Wnt/β-连环蛋白信号通路来抑制细胞糖酵解，抑制细胞增殖和侵袭。牛膝甾酮处理导致E-钙黏蛋白上调并抑制N-钙黏蛋白表达。此外,牛膝甾酮处理损害细胞活力、侵袭能力和细胞内糖酵解水平，但诱导细胞凋亡。BML 284的给药逆转了牛膝甾酮的抑制作用。此外，牛膝甾酮在裸鼠异种移植模型中抑制了OS细胞的肿瘤发生。
我们的研究揭示了牛膝甾酮的抗癌作用，包括增殖抑制、细胞侵袭抑制和糖酵解损伤。这些作用似乎是通过靶向Wnt/β-连环蛋白信号通路来实现的。这些数据表明，牛膝甾酮可能被开发成为一种潜在的骨肉瘤治疗药物。
