Extract of Platycodon grandiflorum Prevents Doxorubicin-induced Cardiotoxicity in Breast Cancer

Figure 1.. PG ameliorated Dox-induced cardiac dysfunction in mice with breast cancer. Echocardiographic assay was used to determine the attenuated left ventricular dysfunction of PG on Dox-induced cardiac dysfunction in mice. PG treatment (1 and 2 g/kg/day) significantly attenuated left ventricular dysfunction in Dox-treated mice as indicated by the increased LVEF and LVFS (A and B). *P < .05 versus the control group; #P < .05 versus the Dox group.

Figure 2.. PG reduced Dox-induced inflammatory and oxidation factors in mice with breast cancer. ELISA was conducted to determine the inflammatory and oxidation factors in serum. Intuitive quantitative chart analysis showed that PG reduced the levels of inflammatory and oxidation factors (A and B). **P < .01 versus the control group; #P < .05, ##P < .01 versus the Dox group.

Figure 3.. PG reduced Dox-induced myocardial fibrosis and collagen deposition in mice with breast cancer. (A) Masson’s trichrome staining and IHC showed that PG reduced Dox-induced myocardial fibrosis and collagen deposition. (B) Intuitive quantitative chart analysis showed the percentage of the area with collagen type I and III staining. **P < .01 versus the control group; ##P < .01 versus the Dox group. Images were obtained at 400× magnification.

Figure 4.. PG inhibited Dox-induced apoptosis in the myocardium of mice with breast cancer. (A) Western blot analysis was performed to detect the relative protein expression levels. GAPDH was used as a control. After PG treatment in mice with breast cancer, the expression of apoptosis-related proteins changed; for instance, Bcl-2/Bax and Bcl-XL increased, whereas cytochrome C and cleaved caspase-3 decreased (B). All experiments were performed in triplicate. *P < .05, **P < .01 versus the control group; #P < .05, ##P < .01 versus the Dox group.

Figure 5.. PG enhanced the antimetastatic efficacy of Dox in a breast cancer mouse model. The weight and size of the primary tumor were measured (A and B). The number of lung metastatic nodules was obviously reduced (C and D). **P < .01 versus the control group; #P < .05 versus the Dox group.

Figure 6.. Molecular mechanism of PG plus Dox in suppressing tumor metastasis in vivo. PG downregulated the protein expression of MMP2 and MMP9 but upregulated the expression of TIMP2 and TIMP3 in lung metastatic tumor tissues (A and B). GAPDH was used as a control. All experiments were performed in triplicate. *P < .05, **P < .01 versus the control group; #P < .05, ##P < .01 versus the Dox group.

Figure 7.. Immunohistochemical staining of MMP2, MMP9, TIMP2, and TIMP3 in lung metastatic tumor tissues. The positive cells in each group were indicated (A and B). **P < .01 versus the control group; ##P < .01 versus the Dox group. Images were obtained at 400× magnification.