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.
Highlights
Lung cancer is one of the most common malignancies in the world with survival period less than 5 years[1]
Shenqi Fuzheng (SQFZ) injection is widely used in clinic as an adjuvant therapy in treating lung cancer, esophagus cancer and
The target prediction of SQFZ injection was based on ingredient determination in 3.1
Summary
Lung cancer is one of the most common malignancies in the world with survival period less than 5 years[1]. The main pharmacological mechanism of docetaxel is binding tubular protein, and making cells stay in the G2/M phase[6]. It has the effect of anti-tumor angiogenesis and apoptosis[7,8]. When in combination with docetaxel, SQFZ injection could enhance docetaxel’s efficacy on A549 and Lewis lung cancer cell[15]. Network pharmacology is a new discipline based on the characteristics of biological molecules It based on multiple authoritative databases which allows us to form an initial understanding of the mechanisms of medicine and diseases. We develop a network pharmacology analysis to identify SQFZ injection’s mechanism in anti-cancer as well as drug-drug interaction with docetaxel. Conduct in vivo and in vitro experiment based on the results of network pharmacology analysis
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