Anti-tumor Effects Research Of Andrographis Effective Parts Combined With Chemotherapy Drugs

Objective: Chemotherapy drugs play an important role on the cancer treatment.By killing tumor cells,chemotherapy drugs could produce cytotoxicity towards normal cells and cause strong side effects,consequently affectting the life quality of patients.With the concept being widely accepted,which is “survival with tumor,attention to the quality of life”,the combination of chemotherapy drugs and traditional Chinese medicine have been used clinically.For example,Astragalus particles,Fufangkushen injection,Zhenqifuzheng capsules and other drugs have been used as an adjunct drugs in the treatment of cancer.Traditional Chinese medicine could enhance the efficacy of chemotherapy as well as improve immune function by reducing the side effects caused by chemotherapy,thereby improving the life quality and prolong survival time of the patients.Vinorelbine(NVB)was used to cure non-small cell lung cancer and its significant side effects were marrow suppression.Adriamycin(ADM)was a broad-spectrum anti-tumor medicine,which could easily lead to cardiac toxicity.In our previous studies,the effective parts of andrographis paniculata(AEP)could significantly inhibit the proliferation of lung cancer Lewis,breast cancer 4T-1 of the mice.Its mechanism is mainly through the the two-way adjustment towards TGF-β1,AEP could improve the quality of life and prolong survival time of the mice.The purpose of this paper was to investigate the combination of AEP and NVB towards Lewis lung cancer of mice,and the combination of AEP and ADM towards 4T-1 breast cancer of mice,thus to explore AEP function towards chemotherapy drugs.Methods: The model of subcutaneously transplanted was established towards Lewis lung cancer of the C57BL/6 mice and breast cancer 4T-1 of the BABL/C mice.They were randomly divided into eight groups: the negative control group(NS,0.2 m L/10 g),NVB or ADM group(5 mg/kg),AEP high-dose group(400 mg/kg),AEP medium-dose group(200 mg/kg),AEP low-dose group(100 mg/kg),the combination group of high-dose(400 mg/kg + 5 mg/kg),the combination group of middle-dose(200 mg/kg + 5 mg/kg),thecombination group of low-dose(100 mg/kg + 5 mg/kg).NS,AEP were gavaged once a day;chemotherapy drugs were used intravenously administered once a week.By recording the general state of the mice,spontaneous activity,survival time,quality of life of mice;By calculating tumor volume,tumor inhibition and the synergistic rate index,we evaluate the anti-tumor effect of AEP combination with chemotherapy drug on Lewis lung cell and breast cancer 4T-1.By calculating the index of the organs of mice,we evaluate the impact of drugs on immune organs of mice;By the examination of peripheral blood,we evaluate the impact of drugs on hermatopoietic function;By detecting the tumor-specific biochemical indicators(AST/GOT,LDH,γ-GT,AKP,5,-NT)in serum and oxidative enzymes(SOD,MDA)vitality through biochemical methods,we evaluate the impact of drugs on the body tissue damage and antioxidant systems;HE staining was used to observe pathological changes of tumor and tissue.Results: The therpy of AEP combined NVB towards Lewis lung cancer of mice,AEP high,medium,low-dose group and NVB group,the tumor inhibition rate of Lewis lung tumor was 53.16%,51.15%,43.52%,57.18%;combined group high,medium and low-dose inhibition rate was 86.52%,82.46%,73.36%,Q values were 1.08,1.05,0.97,compared with the negative control group,there are significant differences(P <0.01).The survival period showed that the combined group of high,medium and low doses prolonged the life of mice with Lewis lung cancer was 112.7%,107.2%,98.2%.The body weight,locomotor activity of the mice in NVB group declined in varying degrees(P <0.05),other groups were not significantly different.According to blood reference values,AEP high,medium and low-dose and medium-dose combination group makes PLT count within the normal range.WBC,RBC count is within the normal range of thr joint group with high-dose.Compared with the chemotherapy drug group,combination groups of high and medium-dose significantly increased SOD vitality in mice(P <0.05);High-dose combination group reduced the content of MDA significantly in mice(P <0.05).AEP high,medium and low-dose group and the combined group could reduce the activity of 5,-NT,AST / GOT,γ-GT,AKP significantly(P <0.05).Pathological analysis showed that the density and morphology of tumor cell changed,the tumor cell morphology of the combined group pyknoticed,nuclei lysis occurred and there was a lot of inflammation,necrosis and so on.Compared with NVB group,the liver tissue of combination group was dense,neat,central venous dilation.The therpy of AEP combined ADM towards breast cancer 4T-1 of mice,AEP high,medium,low-dose group and ADM group,inhibition rate towards breast cancer 4T-1 was 37.55%,40.19%,21.15%,51.91%;combined group high,medium and low-dose inhibition rate was 73.31,70.19%,68.09%,Q values were 1.04,0.99,1.10,compared with the negative control group,there are very significant differences(P <0.01).The body weight,locomotor activity of the mice in ADM group declined in varying degrees.The SOD vitality of combination groups increased significantly,the content of MDA reduced significantly.The activity of LDH,AST/GOT,γ-GT,AKP reduced significantly.Compared with the negative control group,the combined group showed no significant changes in cardiac cell morphology.Conclusion: The combination of AEP and chemotherapy drugs NVB,ADM could enhance the anti-tumor activity towards Lewis lung cancer,breast cancer 4T-1,improving the bone marrow suppression and hematopoietic disorders caused by NVB,reducing cardiac toxicity caused by ADM,which might be related to the less release of AST/GOT,LDH,γ-GT,AKP,5,-NT levels in serum,improving the immune function,life quality and prolonging survival time of mice.