Effects of Xiangcao Fuzheng Mixture on tumor angiogenesis and gene expression of glycolytic related enzymes HK2 and LDH-A in Lewis lung cancer mice
Objective:To investigate the mechanism of anti-tumor effect of Xiangcao Fuzheng Mixture(XCFZ)on Lewis lung cancer mice.Methods:Lewis lung cancer cell line culture and transplantation method was used to establish a lung cancer tumor bearing mouse model,which was randomly divided into model group(M),chemotherapy group(DDP),XCFZ low(LD),medium(MD),high dose group(HD),and combined group(MD+DDP),with 10 mice in each group.From the second day of modeling,the LD,MD,HD were gavaged XCFZ 0.93,1.86 and 3.72 g/mL,respectively.DDP was intraperitoneally injected with 0.64 mg/mL cisplatin solution 0.1 mL/2 d,and was intragastatically administrated with 0.2 mL/d double steaming water.The MD+DDP was administrated with XCFZ medium dose intragastrium combined with intraperitoneal injection of cisplatin.The model group was administrated with 0.9％sodium chloride solution once a day for 14 days.The body weight,tumor weight,spleen and thymus weight of the mice were weighed,and the tumor inhibitory rate and spleen thymus index were calculated.The mRNA expressions of HK2 and LDH-2 in tumor tissues were detected by qRT-PCR,and the expressions of VEGFR-2,VEGF,PI3K and Akt in tumor tissues were detected by immunohistochemistry and Western Blot.Results:The tumor inhibition rate of MD+DDP group was the highest,followed by DDP group and MD group.Compared with M group,spleen index in XCFZ high-dose and medium-dose groups and MD+DDP groups was significantly increased(P＜0.01,P＜0.05),thymus index in XCFZ high-dose and medium-dose groups was significantly increased(P＜0.01,P＜0.05),spleen index and thymus index in DDP group was significantly decreased(P＜0.01,P＜0.05).Compared with the DDP group,the thymus index of all XCFZ dose groups and the MD+DDP group was significantly increased(P＜0.05,P＜0.01),and the spleen index of XCFZ middle and high dose groups and the MD+DDP group was significantly increased(P＜0.01).XCFZ treatment groups had more nucleolar shrinkage,cell death and nuclear fragmentation.In the cisplatin group,the tumor cells were smaller,the nuclear division phenomenon and heterotypic cells were rare,and the necroclastic cells were more.Compared with the M group,the expression levels of LDH-A and HK2 mRNA in each dose of XCFZ group,cisplatin group and combination group were significantly decreased(P＜0.05,P＜0.01).Compared with the DDP group,the expression level of LDH-A mRNA in the combination group was significantly decreased(P＜0.05).Compared with the M group,the expressions of VEGFR-2,VEGF,PI3K and Akt protein in tumor tissues of XCFZ medium and high dose groups,DDP group and MD+DDP group were significantly decreased(P＜0.0l,P＜0.05).Compared with the DDP group,the expressions of VEGFR-2,VEGF,PI3K and Akt protein in the combination group were significantly decreased(P＜0.05,P＜0.01).Conclusion:XCFZ combined with Cisplatin can improve immune function,enhance efficacy and reduce toxicity in Lewis lung cancer mice.The mechanism is to interfere with VEGFNEGFR-2 anti-tumor angiogenesis through PI3K/Akt pathway,and down-regulate the expression of glycolytic LDH-A gene to inhibit the proliferation and metastasis of lung cancer.
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