研究动态
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白花丹素对 TSCC PDX 模型的生长具有抑制作用,并增强顺铂的抗癌功效。

Plumbagin has an inhibitory effect on the growth of TSCC PDX model and it enhances the anticancer efficacy of cisplatin.

发表日期:2023 Nov 03
作者: Yuqi Xin, Qingkun Jiang, Chenshu Liu, Jiaxuan Qiu
来源: Cellular & Molecular Immunology

摘要:

头颈鳞状细胞癌是全球第六大常见恶性肿瘤。舌鳞状细胞癌是该类型常见的恶性肿瘤,预后差、复发率高、生存率低。白花丹素来源于白花丹(Plumbago zeylanica L),多项研究报告白花丹素可以抑制细胞、肿瘤转移、诱导多种癌细胞凋亡。患者来源的异种移植(PDX)模型可以维持人类肿瘤的异质性和微环境,是开发潜在有效的TSCC治疗方法的有力研究工具。将从TSCC患者获得的肿瘤组织植入免疫缺陷小鼠体内建立TSCC PDX模型。随后,利用PDX模型评估白花丹素对TSCC的抗肿瘤作用。此外,我们进行了下一代测序(NGS)并探索了治疗组和对照组之间的 mRNA 表达谱。我们选取了8个与TSCC患者特征和预后相关的mRNA进行进一步分析。白花丹素能够抑制TSCC PDX模型的生长并抑制Akt/mTOR通路的表达。此外,白花丹素被证明可以增加对顺铂的药物敏感性。选择用于进一步分析的 8 个 mRNA,AXL、SCG5、VOPP1、DCBLD2 和 DRAM1 是促癌基因,DUSP1、AQP5 和 BLNK 是抑癌基因。与TSCC患者的诊断、生长、预后及免疫细胞浸润等相关。白花丹素对TSCC PDX模型的生长具有抑制作用。此外,白花丹素增强顺铂的抑制作用。
Head and neck squamous cell carcinomas are the sixth most common malignant tumors worldwide. Tongue squamous cell carcinoma is a common malignant tumor of this type, and it is associated with poor prognosis, a high rate of recurrence and a low survival rate. Plumbagin is derived from Plumbago zeylanica L, several studies report that plumbagin could inhibit cell, tumor metastasis, induce apoptosis in various cancer cells. Patient-derived xenograft (PDX) model can maintain the heterogeneity and microenvironment of human tumors, is a powerful research tool for developing potentially effective therapies for TSCC.Tumor tissues obtained from TSCC patients were implanted into immunodeficient mice to establish TSCC PDX models. Subsequently, the PDX models were used to evaluate the anti-tumor effects of plumbagin on TSCC. Furthermore, we conducted next-generation sequencing (NGS) and explored the mRNA expression profiles between the treatment and control groups. We selected eight mRNAs related to the characteristics and prognosis of TSCC patients for further analysis.Plumbagin could inhibit the growth of TSCC PDX models and inhibit expression of Akt/mTOR pathway. In addition, plumbagin was shown to increase drug sensitivity to cisplatin. The eight mRNAs selected for further analysis, AXL, SCG5, VOPP1, DCBLD2 and DRAM1 are cancer-promoting genes, DUSP1, AQP5 and BLNK are cancer suppressor genes. And they were related to the diagnosis, growth, prognosis, and immune cell infiltration in TSCC patients.Plumbagin exhibits an inhibitory effect on the growth of the PDX model of TSCC. Moreover, plumbagin enhances the inhibitory effects of cisplatin.