Impacts of Fuzhengxiaoyan decoction on immune functions in nude mice bearing EMT-6 breast cancer

Objective: The aim of this study was to observe the impacts of Fuzhengxiaoyan decoction (FZXY) on the immune functions in nude mice bearing EMT-6 breast cancer (EMT-6-carryring mice). Materials and Methods: The successfully prepared EMT-6 breast cancerbearing nude mice models were randomly divided into three groups (n=20): the treatment group: orally administrated FZXY, the control group: orally administrated the Shenmai injection, and the model group: orally administrated an equal volume of normal saline, twice a day for consecutive 14 days. Results: The mice in each group were then sacrificed and their spleen and thymus indexes were compared; ELISA was performed to detect the content changes of TGF-β and IL-6 in the spleens. FZXY could significantly increase the spleen and thymus indexes in these EMT-6-carrying mice when compared with the model group (p < 0.05); meanwhile, the contents of IL-6 and TGF-β in the spleens of the FZXY group were significantly decreased (p < 0.05), similar to those in the positive control group (Shenmai injection). Conclusion: FZXY could improve the immune functions of EMT-6- bearing mice, which was the mechanism of this prescription towards inhibiting breast cancer.

Fuzhengxiaoyan decoction; Spleen index; Thymus index; IL-6; TGF-β.

[1] Ghoncheh M., Mirzaei M., Salehiniya H.: “Incidence and Mortality of Breast Cancer and their Relationship with the Human Development Index (HDI) in the World in 2012”. Asian Pac. J. Cancer Prev., 2016, 16, 8439.

[2] Zheng Y., Zhang M.: “Disparities of breast cancer burden between China and western countries and its implication”. Zhonghua wai ke za zhi, 2016, 53, 905.

[3] Harms M.W., Budach W., Dunst J., Feyer P., Fietkau R., Haase W., et al.: “DEGRO practical guidelines for radiotherapy of breast cancer VI: therapy of locoregional breast cancer recurrences”. Strahlenther Onkol., 2016, 192, 199.

[4] Kim S.W., Goedegebuure P., Gillanders W.E.: “Mammaglobin-A is a target for breast cancer vaccination”. Oncoimmunology, 2016, 5, e1069940.

[5] Wei X., Hu D.H., Yi M.H., Chang X.L., Zhu W.J., Qu S.L., et al.: “Construction and analysis of a breast cancer gene-drug network model”. Nan Fang Yi Ke Da Xue Xue Bao, 2016, 36, 170.

[6] Zhou W., Gao Y., Xu S., Yang Z., Xu T.: “Purification of a mannose- binding lectin Pinellia ternata agglutinin and its induction of apoptosis in Bel-7404 cells”. Protein Expr. Purif., 2014, 93, 11.

[7] Schaffer M., Schaffer P.M., Zidan J., Bar Sela G.: “Curcuma as a functional food in the control of cancer and inflammation”. Curr. Opin. Clin. Nutr. Metab. Care, 2011, 14, 588.

[8] Chaithongyot S., Asgar A., Senawong G., Yowapuy A., Lattmann E., Sattayasai N., et al.: “Anticancer Effects of Curcuma C20-Dialdehyde against Colon and Cervical Cancer Cell Lines”. Asian Pac. J. Cancer Prev., 2015, 16, 6513.

[9] De Simone V., Franzè E., Ronchetti G., Colantoni A., Fantini M.C., Di Fusco D., et al.: “Th17-type cytokines, IL-6 and TNF-α synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth”. Oncogene, 2015, 34, 3493.

[10] Mauer J., Denson J.L., Brüning J.C.: “Versatile functions for IL-6 in metabolism and cancer”. Trends Immunol., 2015, 36, 92.

[11] Sağlam Ö., Ünal Z.S., Subaşı C., Ulukaya E., Karaöz E.: “IL-6 originated from breast cancer tissue-derived mesenchymal stromal cells may contribute to carcinogenesis”. Tumour. Biol., 2015, 36, 566.

[12] Heo T.H., Wahler J., Suh N.: “Potential therapeutic implications of IL-6/IL-6R/gp130-targeting agents in breast cancer”. Oncotarget, 2016, 7, 15460.

[13] Morrison C.D., Schiemann W.P.: “Tipping the balance between good and evil: Aberrant 14-3-3ζ expression drives oncogenic TGF-β signaling in metastatic breast cancers”. Breast Cancer Res., 2015, 17, 92.

[14] Mcandrews K.M., Mcgrail D.J., Ravikumar N., Dawson M.R.: “Mesenchymal Stem Cells Induce Directional Migration of Invasive Breast Cancer Cells through TGF- β”. Sci. Rep., 2015, 5, 16941.

[15] Ma Y., Liu H., Zhang H., Shao R.G.: “The TGF-β signaling pathway induced EMT in breast cancer”. Yao Xue Xue Bao, 2015, 50, 385.

[16] Neuzillet C., Tijeras-Raballand A., Cohen R., Cros J., Faivre S., Raymond E., et al.: “Targeting the TGFβ pathway for cancer therapy”. Pharmacol. Ther., 2015, 147, 22.

[17] Zhou F., Drabsch Y., Cohen R., Cros J., Faivre S., Raymond E., et al.: “Nuclear receptor NR4A1 promotes breast cancer invasion and metastasis by activating TGF-β signalling”. Nat. Commun., 2014, 5, 3388.

[18] Barreto S.C., Hopkins C.A., Bhowmick M., Ray A.: “Extracellular matrix in obesity - cancer interactions”. Horm. Mol. Biol. Clin. Investig ., 2015, 22, 63.

[19] Ye J., Wu D., Wu P., Chen Z., Huang J.: “The cancer stem cell niche: cross talk between cancer stem cells and their microenvironment”. Tumour. Biol., 2014, 35, 3945.

[20] Qiu Q., Su Y., Zheng Y., Cai H., Wu S., Lu W., et al.: “Increased pSmad2 expression and cytoplasmic predominant presence of TGF- βRII in breast cancer tissue are associated with poor prognosis: results from the Shanghai Breast Cancer Study”. Breast Cancer Res. Treat., 2015, 149, 467.

[21] Novitskiy S.V., Forrester E., Pickup M.W., Gorska A.E., Chytil A., Aakre M., et al.: “Attenuated transforming growth factor beta signaling promotes metastasis in a model of HER2 mammary carcinogenesis”. Breast Cancer Res., 2014, 16, 425.