Tumor inhibitory effects of Sanchong Tongluo Sanjie Formula on Lewis lung cancer mice based on MAPK pathway
Objective To study the tumor inhibitory effects of Sanchong Tongluo Sanjie Formula(SCTLSJF)on Lewis lung cancer mice and its regulatory effects on the mitogen-activated protein kinase(MAPK)signaling pathway.Methods A total of 48 C57BL/6 mice were selected,and six of them were randomly assigned to the blank group.The remaining 42 C57BL/6 mice were used to establish the Lewis lung cancer-bearing mouse model,and were then randomized into model group(normal saline),positive control group(Cisplatin Injection 2 mg/kg),low-dose powder group(SCTLSJF powder 0.45g/kg),high-dose powder group(SCTLSJF powder 1.8 g/kg),low-dose powder+cisplatin group(SCTLSJF powder 0.45 g/kg+Cisplatin Injection 2 mg/kg),low-dose decoction group(SCTLSJF decoction 3.9 g/kg),and high-dose decoction group(SCTLSJF decoction 15.6 g/kg),with six mice in each group.Samples were collected 14 days after administration.The tumor suppression rate and tumor-free body mass were calculated.HE staining was used to observe the pathological changes of the subcutaneous xenograft tumor,lung tissues,and liver tissues;qPCR was employed to determine the mRNA expressions of extracellular regulated protein kinases(Erk),hypoxia inducible factor-1α(HIF-1α),p38 protein(p38),vascular endothelial growth factor A(VEGFA),c-Jun N-terminal kinase(JNK),and matrix metalloproteinase 2(MMP-2)in the subcutaneous xenograft tumor,while Western blot to examine the protein expressions of them.Results(1)Compared with the model group,the xenograft tumor mass in the positive control,low-dose powder+cisplatin,and high-dose powder groups was lower(P<0.05).Compared with the low-dose powder group,the xenograft tumor mass was lower in the high-dose powder group(P<0.05).Compared with the positive control group,the tumor-free body mass was higher in all pure Chinese medicine groups and model group(P<0.05).(2)The HE staining of lung tissues showed that the low-dose powder+cisplatin group exhibited a higher degree of tumor cell necrosis;in all pure Chinese medicine groups,nuclear division was rarely observed,and the number of tumor metastases was lower compared to the model group.The HE staining of liver tissues showed that no significant tumor lesions were observed in the low-dose powder+cisplatin and positive control groups;the tumor metastasis foci in the high-dose powder and high-dose decoction groups were relatively small in volume.(3)Compared with the model group,the mRNA expressions of Erk and p38 in the subcutaneous xenograft tumor tissues in the other cancer-bearing groups decreased(P<0.05).The expression of JNK mRNA also decreased in the low-dose powder+cisplatin,low-dose powder,low-dose decoction,and high-dose decoction groups(P<0.05).Compared with the positive control group,the low-dose powder+cisplatin group and all pure Chinese medicine groups showed a decrease in JNK mRNA expression in the subcutaneous xenograft tumor tissues(P<0.05).(4)Compared with the model group,the protein expression level of Erk decreased in the positive control,low-dose powder,and high-dose decoction groups(P<0.05),the protein expression levels of p38 and HIF-1α decreased in the positive control,low-dose powder+cisplatin,low-dose powder,high-dose powder,and high-dose decoction groups(P<0.05),and the protein expression level of JNK decreased in the other cancer-bearing groups(P<0.05).Conclusion SCTLJSF has certain inhibitory effects on Lewis lung cancer in mice,with the high-dose powder group showing the superior tumor inhibitory efficacy.The mechanism may be related to the inhibition of MAPK signaling pathway.
Lewis lung cancer cellsSanchong Tongluo Sanjie Formulalung cancermitogen-activated protein kinase signaling pathwaytumor inhibitory effects