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. 2019 Mar 14;9(1):4533.
doi: 10.1038/s41598-019-40954-3.

Network Pharmacology-Based identification of pharmacological mechanism of SQFZ injection in combination with Docetaxel on lung cancer

Tan Li  1 , Zhu Baochen  1 , Zhang Yue  2 , Wang Cheng  1 , Wu Yali  1 , Sun Zongxi  1 , Zhang Wantong  3 , Lu Yang  4 , Du Shouying  5
Affiliations

Network Pharmacology-Based identification of pharmacological mechanism of SQFZ injection in combination with Docetaxel on lung cancer

Tan Li et al. Sci Rep. .

Abstract

Docetaxel is the widely-used first-line therapy to treat lung cancer around the world. However, tumor progression and severe side effect occurred in some patients with docetaxel treatment. Most of the side effects were caused by immunocompromise, which limits the long-term use of docetaxel. Shenqi Fuzheng (SQFZ) injection has been used as adjuvant therapy to treat lung cancer which may enhance immunity as well. Owing to the complexity of drug combination, the mechanism of SQFZ injection in combination with docetaxel on lung cancer remains unclear. Therefore, a network pharmacology-based strategy was proposed in this study to help solve this problem. Network pharmacology approach comprising multiple components, candidate targets of component and therapeutic targets, has been used in this study. Also, in vivo and in vitro experiment was applied to verify the predicted targets from network pharmacology We established mouse lung cancer model and inject with docetaxel and SQFZ injection. Tumour weight, spleen index, thymus index, immunohistochemical staining and ELISA were conducted to evaluate the effect and underlying mechanisms of docetaxel and SQFZ injection. Besides A549 cells were also administrated by docetaxel and SQFZ.The indexes BCL2, CASP3 and CASP9 were determined after administration. The results indicated that combination of SQFZ and docetaxel could reduce tumour weight, enhance the spleen index, thymus index. Meanwhile, it could improve the activity of caspase-3 and IL-2 in mice and caspase-3, caspase-9 in A549 cell and inhibit the activity of BCL-2 in A549 cell, which verified the potential protective targets predicted by network pharmacology. In conclusion, combination of SQFZ and docetaxel could increase the curative effect by inducing tumour to apoptosis and play a key role on immunoprotection to reduce side effects.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
UPLC-MS results of SQFZ injection ((A,B) is the results of negative ionization mode; (C,D) is the results of positive ionization mode).
Figure 2
Figure 2
Network of the 11 compounds in SQFZ injection predicted to have 182 candidate targets.
Figure 3
Figure 3
Network of docetaxel predicted to have 452 candidate targets.
Figure 4
Figure 4
Network of docetaxel, SQFZ injection and lung cancer predicted to have 40 common potential targets.
Figure 5
Figure 5
Mice subcutaneous lung cancer model.
Figure 6
Figure 6
Result of thymus index. *p < 0.05 compared to control group.
Figure 7
Figure 7
Result of spleen index. *p < 0.05 compared to control group.
Figure 8
Figure 8
Result of tumour weight. *p < 0.05 compared to control group.
Figure 9
Figure 9
Immunohistochemical staining results of each group (A: control group; B: docetaxel group; C: SQFZ + docetaxel group).
Figure 10
Figure 10
Result of caspase-3 activity. *p < 0.05 compared to control group. △p < 0.05 compared to docetaxel group.
Figure 11
Figure 11
Result of IL-2 activity.
Figure 12
Figure 12
Results of western-blot analysis.
Figure 13
Figure 13
Result of BCL-2 activity *p < 0.05 compared to control group; Δp < 0.05 compared to SQFZ group; ※p < 0.05 compared to docetaxel group.
Figure 14
Figure 14
Result of caspase-3 activity *p < 0.05 compared to control group; △p < 0.05 compared to SQFZ group; ※p < 0.05 compared to docetaxel group.
Figure 15
Figure 15
Result of caspase-9 activity. *p < 0.05 compared to control group; △p < 0.05 compared to SQFZ group; ※p < 0.05 compared to docetaxel group.
See this image and copyright information in PMC

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