Department of Interventional Radiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China.
Int J Mol Med. 2018 Sep;42(3):1569-1576. doi: 10.3892/ijmm.2018.3722. Epub 2018 Jun 7.
Although plumbagin, a natural naphthoquinone, has exhibited antiproliferative activity in numerous types of cancer, its anticancer potential in esophageal squamous cell carcinoma (ESCC) remains unclear. In the present study, the effect of plumbagin on the growth of ESCC cells was investigated in vitro and in vivo. ESCC cells were treated with plumbagin and tested for cell cycle distribution and apoptosis. The involvement of STAT3 signaling in the effect of plumbagin was examined. The results demonstrated that plumbagin treatment suppressed ESCC cell viability and proliferation, yet normal esophageal epithelial cell viability was not affected. Plumbagin treatment increased the proportion of cells in the G0/G1 phase of the cell cycle and decreased the proportion of cells in the S phase. Furthermore, plumbagin‑treated ESCC cells displayed a significantly greater % of apoptotic cells. Western blot analysis confirmed that plumbagin upregulated tumor protein p53 and cyclin‑dependent kinase inhibitor 1A (also known as p21), while it downregulated cyclin D1, cyclin‑dependent kinase 4, and induced myeloid leukemia cell differentiation protein Mcl‑1. Mechanistically, plumbagin inhibited STAT3 activation, and overexpression of constitutively active STAT3 reversed the plumbagin‑mediated growth suppression in ESCC cells. In vivo studies demonstrated that plumbagin delayed the growth of ESCC xenograft tumors and reduced STAT3 phosphorylation. Overall, plumbagin was demonstrated to target STAT3 signaling and to inhibit the growth of ESCC cells both in vitro and in vivo, suggesting that it may represent a potential anticancer agent for ESCC.
虽然天然萘醌化合物白花丹素已在多种类型的癌症中显示出抗增殖活性，但它在食管鳞状细胞癌（ESCC）中的抗癌潜力尚不清楚。在本研究中，研究了白花丹素在体外和体内对 ESCC 细胞生长的影响。用白花丹素处理 ESCC 细胞，检测细胞周期分布和细胞凋亡。研究了 STAT3 信号通路在白花丹素作用中的参与。结果表明，白花丹素处理抑制 ESCC 细胞活力和增殖，但正常食管上皮细胞活力不受影响。白花丹素处理增加了细胞周期 G0/G1 期的细胞比例，降低了 S 期的细胞比例。此外，白花丹素处理的 ESCC 细胞显示出更高比例的凋亡细胞。Western blot 分析证实，白花丹素上调肿瘤蛋白 p53 和细胞周期蛋白依赖性激酶抑制剂 1A（也称为 p21），同时下调细胞周期蛋白 D1、细胞周期蛋白依赖性激酶 4，并诱导髓样白血病细胞分化蛋白 Mcl-1。从机制上讲，白花丹素抑制 STAT3 激活，而过表达组成性激活的 STAT3 逆转了白花丹素介导的 ESCC 细胞生长抑制。体内研究表明，白花丹素延迟 ESCC 异种移植肿瘤的生长并降低 STAT3 磷酸化。总体而言，白花丹素被证明靶向 STAT3 信号通路并抑制 ESCC 细胞的体外和体内生长，表明它可能是 ESCC 的一种潜在抗癌药物。
