Experimental Study on Effect of Modified Guilu Erxianjiao Decoction Combined with Cisplatin on Resistance-related Genes and IL-7-mediated Wnt/β-catenin Signaling Pathway in Mice with Lewis Lung Cancer / 中国实验方剂学杂志

ABSTRACT

Objective:To observe the effect of modified Guilu Erxianjiao decoction combined with cisplatin on the immune function， resistance-related genes and interleukin-7（IL-7）-mediated Wnt/<italic>β</italic>-serial protein（<italic>β</italic>-catenin）signaling pathway in Lewis lung cancer mice by establishing a mouse model of Lewis lung cancer with deficiency of both Qi and Yin. And the anti-cancer mechanism of modified Guilu Erxianjiao decoction was clarified， so as to provide a basis for its clinical application. Method:A Lewis lung cancer mouse model （type of deficiency of both Qi and Yin） was established. Mice were divided into a normal group （no modeling）， a model group （saline solution）， a cisplatin group （cisplatin， 2 mg·kg^-1）， a traditional Chinese medicine （TCM） group （modified Guilu Erxianjiao decoction， 19.63 g·kg^-1·d^-1）， and a combined group （modified Guilu Erxianjiao decoction， 19.63 g·kg^-1·d^-1 + cisplatin， 2 mg·kg^-1）. The 10 mice in each group were administered separately for 21 days of intervention. The general conditions and organ indexes of mice were observed， and tumor inhibition rate was calculated. CD4⁺CD25⁺ regulatory T cell （CD4⁺CD25⁺ Treg） were detected by flow cytometry， the IL-7 level of cytokines in serum was detected by enzyme linked immunosorbent assay（ELISA）， and real-time quantitative polymerase chain reaction（Real-time PCR） was used to detect the gene expression level of drug resistance-related genes P-glycoprotein（P-gp）， and multidrug resistance protein1（MRP1）in tumor tissues. The protein expression of Wnt/<italic>β</italic>-serial protein（<italic>β</italic>-catenin）signaling pathway in tumor tissues were detected by Western blot. Result:In the TCM group and the combined group， the food intake increased， the mental state was better， the response was sensitive， and the body weight increased. Compared with the cisplatin group， the thymus index and spleen index in the combined group were significantly increased （<italic>P</italic><0.01）， and the tumor inhibition rate of the combined group was significantly increased （<italic>P</italic><0.01）. Compared with the cisplatin group， the percentage of CD4⁺CD25⁺Treg/CD4⁺ in the TCM group and the combined group was significantly reduced （<italic>P</italic><0.01）， and IL-7 in the TCM group and the combined group was significantly increased （<italic>P</italic><0.01）. Compared with the cisplatin group， the expressions of P-gp and MRP1 genes in the TCM group and the combined group were significantly reduced （<italic>P</italic><0.05， <italic>P</italic><0.01）， and the protein expressions of secretory glycoprotein1（Wnt1）and <italic>β</italic>-serial protein（<italic>β</italic>-catenin）in the TCM group and the combined group were significantly reduced （<italic>P</italic><0.01）. Conclusion:The combined use of modified Guilu Erxianjiao decoction and cisplatin can significantly inhibit the growth of tumors in mice with Lewis lung cancer， and its mechanism of action may be related to the efficacy of m odified Guilu Erxianjiao decoction in relieving the body's immunosuppressive state， promoting the body to produce IL-7， regulating IL-7-mediated Wnt/<italic>β</italic>-catenin signaling pathway and reducing the expression of resistance-related genes in lung cancer tissues.