Effect of Qi-Zhen-Gui-Pi decoction on biological behavior of lymphoma cells and its mechanism
10.3781/j.issn.1000-7431.2019.11.081
- Author:
Ying ZHANG
1
Author Information
1. Department of Hematology, Renji Hospital, Shanghai Jiao Tong University School of Medicine
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Cell movement;
Cell proliferation;
Lymphoma;
Phytotherapy
- From:
Tumor
2019;39(5):346-358
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effects of Qi-Zhen-Gui-Pi decoction on the proliferation, apoptosis, cell cycle, migration and invasion of lymphoma cells, and to explore the possible molecular mechanism using high throughput omics technology. Methods: The human lymphoma cell lines (Jurkat, SU-DHL-4, and Raji) were treated with different concentrations of Qi-Zhen-Gui-Pi decoction. The proliferation inhibitory rate of lymphoma cells was detected by CCK-8 method. The changes of apoptosis and cell cycle distribution were detected by FCM assay. The migration and invasion abilities of lymphoma cells were detected by Transwell chamber assay. The gene expression profiles were detected by PrimeView Human Gene Expression Array. Ingenuity Pathway Analysis (IPA) was used to analyze the classical signaling pathway. The expression levels of differentially expressed genes including phosphatidylinositol 3-kinase catalytic subunit alpha (PIK 3CA), nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB 1), inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKBKB), B-cell lymphoma-2 (Bcl -2), Janus kinase 2 (JAK 2) and signal transducer and activator of transcription 3 (STAT 3) were detected by real-time fluorescent quantitative PCR. Results: After the treatment with different concentrations of Qi-Zhen-Gui-Pi decoction (5-25 mg/mL), the proliferation of Jurkat, SU-DHL-4 and Raji cells was significantly inhibited (all P < 0.01). After the treatment with 20 mg/mL and 25 mg/mL Qi-Zhen-Gui-Pi decoction, the apoptosis rates of Jurkat and Raji cells were significantly increased (all P < 0.01). After the treatment with different concentrations of Qi-Zhen-Gui-Pi decoction (10, 15 and 20 mg/ mL) for 48 h, the cell cycle of Jurkat, SU-DHL-4 and Raji cells was arrested in G2/M phase (all P < 0.01). The migration and invasion activities of Jurkat and Raji cells were significantly suppressed by Qi-Zhen-Gui-Pi decoction (15 mg/mL) (all P < 0.01). According to the gene expression profiling data, 648 genes were up-regulated, and 1 022 genes were downregulated after Jurkat cells were treated with Qi-Zhen-Gui-Pi decoction for 48 h. Based on IPA pathway analysis, the phosphoinositide3-kinase (PI3K)/protein kinase B (PKB, Akt) signaling pathway and JAK/STAT signaling pathway were significantly blocked among the enriched pathways of differentially expressed genes (P < 0.001, P < 0.05). The expression levels of PIK3CA, NFKB1, IKBKB, Bcl-2, JAK2 and STAT3 mRNAs were significantly down-regulated (P STAT3 < 0.05, P others < 0.01). Conclusion: Qi-Zhen-Gui-Pi decoction can regulate the biological behavior of lymphoma cell lines, and play an anti-lymphoma role through multiple genes and signaling pathways.
