Investigation on Increase Efficiency of Tanshinones Diterpenoid on Cisplatin and the Related Mechanisms of Anti-lung Cancer
[Objective]To investigate the anti-lung cancer effect of diterpenoid tanshinones(DT),an effective component of Salvia miltiorrhiza,and to verify the synergistic effect of DT on cisplatin and explore the mechanism of DT anti-lung cancer.[Methods]Fifty-six BALB/c nude mice were constructed to A549 lung cancer models and divided into blank group,model group,cisplatin group,DT low-dose group,DT medium-dose group,DT high-dose group Province and cisplatin+DT high-dose group according to different intraperitoneal injection and administration of drugs.Tumor diameter of nude mice was measured and recorded,and tumor volume and inhibitory rate were calculated.The expression of vascular endothelial growth factor A(VEGFA),Ras,cyclin dependent kinase inhibitor 1B(CDKN1B),Bcl-2 associated X(Bax)were detected by Western blot.Real-time quantitative polymerase chain reaction(Real-time qPCR)was used to analyze changes in retinoic acid receptor-related orphan receptor-γt(ROR-γt)and transcription factors forkhead box protein P3(Foxp3).[Results]After DT intervention,the body weight of nude mice with lung cancer increased,inflammatory cell infiltration relieved,metastasis count and tumor volume decreased,tumor inhibition rate increased,indicating DT played a good inhibitory effect on lung cancer transplantation tumors.Compared with blank group,the expression levels of VEGFA and Ras protein in tumor tissue of model group were significantly increased(P<0.01),while the expression levels of CDKN1B and Bax protein were significantly decreased(P<0.01,P<0.05).Compared with model group,the expression levels of VEGFA and Ras protein in cisplatin group,DT low-dose group,DT medium-dose group,DT high-dose group and cisplatin+DT high-dose group were decreased(P<0.01),CDKN1B and Bax protein expression levels were increased(P<0.01,P<0.05).The decrease of oncogene expression and increase of tumor suppressor gene were most obvious in cisplatin+DT high-dose group(P<0.01).Compared with cisplatin group,the expressions of VEGFA and Ras in cisplatin+DT high-dose group were decreased,while the expressions of CDKN1B and Bax were increased,but there was no statistical significance(P>0.05).The higher the dose of DT,the lower the expression level of oncogene and the higher the expression level of tumor suppressor gene was,but there was no statistical significance(P>0.05).Real-time qPCR showed that compared with blank group,the expression levels of ROR-γt and Foxp3 in tumor tissue of model group were significantly increased(P<0.01).Compared with model group,the expression levels of ROR-γt and Foxp3 in tumor tissue of cisplatin group,DT low-dose group,DT medium-dose group,DT high-dose group and cisplatin +DT high-dose group were decreased(P<0.01,P<0.05),and the expression levels of ROR-γt and Foxp3 were decreased most significantly in cisplatin+DT high-dose group(P<0.01).The higher the dose of DT,the lower the expression levels of ROR-γt and Foxp3 were,but there was no statistical significance(P>0.05).[Conclusion]DT has relatively reliable anti-lung cancer efficacy,which is concentration-dependent.DT combined with cisplatin has the tendency to enhance the anti-tumor efficacy of cisplatin.
lung cancerpromoting blood circulation and removing blood stasisditerpenoid tanshinonescisplatinincrease efficiencydose
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