通消阳和颗粒在多柔比星治疗4T1乳腺癌小鼠中的增效减毒作用及其机制研究OA

Objective:To investigate the inhibitory effect and mechanism of Tongxiao Yanghe(通消阳和)Gran-ules combined with doxorubicin on tumors in 4T1 breast cancer-bearing mice and validate the mechanism of Tongxiao Yanghe Granules in alleviating doxorubicin-induced cardiotoxicity in mice,thus providing theoretical and experimental bases for breast cancer treatment with integrated traditional Chinese and Western medicine.Methods:A 4T1 breast cancer-bearing mouse model was established.Successfully modeled mice were assigned into model control,Tongxiao Yanghe Granules(6.82 g/kg),doxorubicin(2.5 mg/kg),doxorubicin+Tongxiao Yanghe Granules(6.82 g/kg and 13.64 g/kg)groups(n=8).Additionally,8 normal mice were selected as the normal control group,and the treatment lasted for 28 days.The general status,body weight,tumor volume,tumor weight,and heart weight were recorded.Hema-toxylin-eosin staining was employed to observe pathological changes in the tumor,lung,and heart tissue.ELISA was em-ployed to measure inflammatory factor levels.Biochemical assays were conducted to measure myocardial enzyme activi-ties.Western blot was employed to assess the protein levels of nuclear factor(NF)-κB,inhibitor of kappa B kinase alpha(IKKα),E-Cadherin,Vimentin,and matrix metalloproteinase(MMP-9)in the tumor tissue and IKKα and inducible ni-tric oxide synthase(INOS)in the myocardial tissue.Results:Compared with the normal control group,the serum levels of tumor necrosis factor(TNF)-α,interleukin(IL)-6,and interferon(IFN)-γ elevated in the model group(P<0.05),and tumor tissues are polymorphic,showed cellular atypia and local fibrous tissue hyperplasia,tumor cell infiltration and tissue destruction in lung tissue,showed dense inflammation.Compared with the model control group,the Tongxiao Yang-he Granules(6.82 g/kg)group and all the combined treatment groups presented reduced tumor mass,increased tumor inhibition rate(P<0.01),declined serum levels of TNF-α,IL-6,and IFN-γ,weakened activities of lactate dehydrogen-ase(LDH),aspartate aminotransferase(AST),and creatine kinase(CK),down-regulated protein levels of Vimentin,MMP-9,NF-κB,and IKKα(P<0.05),up-regulated protein level of E-Cadherin(P<0.01),abnormal tumor structures,tumor cell necrosis,karyorrhexis,karyopyknosis,and reduced tumor cell infiltration and metastasis in the lung tissue.The combined treatment groups demonstrated more significant changes in the above indexes(P<0.05),the doxorubicin(2.5 mg/kg)group demonstrated increased cardiac mass index,and abnormal cardiac muscle structure(P<0.01),ele-vated serum levels or activities of TNF-α,IL-6,IFN-γ,LDH,AST,and CK,up-regulated protein levels of IKKαand INOS in myocardial tissue(P<0.01),which showed myocardial injuryand.Compared with the doxorubicin(2.5 mg/kg)group,the combined treatment groups demonstrated decreased cardiac mass index and tumor mass,increased tumor inhi-bition rate,declined serum levels or activities of TNF-α,IL-6,IFN-γ,LDH,AST,and CK,down-regulated protein levels of IKKα,NF-κB,Vimentin and MMP-9,up-regulated protein level of E-Cadherin in tumor tissue(P<0.05 or P<0.01),and down-regulated protein levels of IKKαand INOS in myocardial tissue(P<0.01).Conclusion:Tongxiao Yanghe Granules combined with doxorubicin can effectively inhibit the proliferation and lung metastasis of 4T1 breast cancer and doxorubicin-induced cardiotoxicity by regulating the expression of NF-κB,INOS,IKKα,Vimentin,MMP-9,and E-Cadherin.