八宝丹通过调节癌症相关基因的转录重编程抑制胰腺癌肿瘤生长。

BaBao Dan Suppresses Tumor Growth of Pancreatic Cancer Through Modulating Transcriptional Reprogramming of Cancer-Related Genes.

作者信息

Song Libin, Fang Zhixiao, Pan Chuanfang, Chen Xiangyuan, Qian Xiang, Cai Yunyun, Zhang Xiumei, Liu Luming

机构信息

Department of Integrative Oncology, Fudan University, Shanghai Cancer Center, Shanghai, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Front Oncol. 2020 Nov 19;10:584330. doi: 10.3389/fonc.2020.584330. eCollection 2020.

DOI:10.3389/fonc.2020.584330

PMID:33330063

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7710661/

Abstract

BACKGROUND AND AIMS

Pancreatic ductal adenocarcinoma (PDAC) is one of refractory malignancies without efficient therapeutics. Babao Dan (BBD) was partially effective to suppress tumor growth of PDAC in clinical practice. However, the molecular mechanisms were unclear.

METHODS

We established PDAC mice models and treated them with BBD through intragastric administration. Treatment and control groups were then subjected to high-throughput RNA sequencing. We presented the transcriptional changes upon BBD treatment by using computational analysis comparing BBD treatment and control groups. Functional enrichment analysis was employed to investigate the biological processes or pathways that BBD modulates.

RESULTS

BBD treatment showed strong suppression on tumor growth of PDAC, even stronger than Gemcitabine. Through differential analysis comparing BBD treatment and control groups, we identified 638 up-regulated and 259 down-regulated genes in the BBD treatment group. BBD was found to activate tumor suppressor genes, such as MTUS1, PDGFB, SOD3, and UCHL1. Furthermore, we revealed that BBD treatment inhibited cancer-related pathways and elevated activities of metabolism-related processes. The BBD-modulated metabolic genes were further showed to be associated with patient survival in an independent cohort with pancreatic cancer.

CONCLUSION

BBD repressed the tumor growth of PDAC. BBD treatment modulated expression of cancer-related genes in PDAC. BBD suppressed cancer-related pathways and activated metabolic processes in PDAC. Our study suggests BBD treatment as potential effective therapeutics for patients with pancreatic cancer.

摘要

背景与目的

胰腺导管腺癌（PDAC）是难治性恶性肿瘤之一，缺乏有效的治疗方法。在临床实践中，八宝丹（BBD）对抑制PDAC肿瘤生长有部分疗效。然而，其分子机制尚不清楚。

方法

我们建立了PDAC小鼠模型，并通过灌胃给予BBD进行治疗。然后对治疗组和对照组进行高通量RNA测序。通过计算分析比较BBD治疗组和对照组，展示BBD治疗后的转录变化。采用功能富集分析来研究BBD调节的生物学过程或途径。

结果

BBD治疗对PDAC肿瘤生长显示出强烈抑制作用，甚至比吉西他滨更强。通过比较BBD治疗组和对照组的差异分析，我们在BBD治疗组中鉴定出638个上调基因和259个下调基因。发现BBD可激活肿瘤抑制基因，如MTUS1、PDGFB、SOD3和UCHL1。此外，我们发现BBD治疗抑制癌症相关途径并提高代谢相关过程的活性。在一个独立的胰腺癌队列中，进一步显示BBD调节的代谢基因与患者生存相关。