Objective To examine the effects of pachyman in combination with vinorelbine and cisplatin on tumor growth and the expression of epidermal growth factor receptor(EGFR)and K-ras in a mouse model of lung cancer induced ...Objective To examine the effects of pachyman in combination with vinorelbine and cisplatin on tumor growth and the expression of epidermal growth factor receptor(EGFR)and K-ras in a mouse model of lung cancer induced using the human lung cancer cell line A549,and to investigate the molecular mechanisms underlying the antitumor effects of pachyman.Methods We recorded the size of the tumor xenografts in mice after treatment with pachyman monotherapy or pachymanin combination with vinorelbine and cisplatin.We performed immunohistochemical analysis to determine the levels of expression and distribution of EGFR and K-ras in lung cancer tissues.Real-time fluorescence quantitative PCR was used to determine the relative mRNA expression levels of EGFR and K-ras in lung cancer tissues.Results Vinorelbine and cisplatin significantly decreased the rate of growth of A549 xenografts,and pachyman increased the efficacy of vinorelbine and cisplatin.EGFR and K-ras were widely expressed in A549 xenografts.Vinorelbine and cisplatin could significantly decrease the expression,distribution and mRNA expression levels of EGFR and K-ras in tumor tissues.Pachyman monotherapy significantly decreased the distribution and the mRNA expression levels of EGFR in lung cancer tissues.In addition,pachyman in combination with vinorelbine and cisplatin markedly decreased the distribution and expression levels of EGFR in lung cancer tissues.However,pachyman monotherapy or combination therapy did not significantly decrease the mRNA expression levels of K-ras.Conclusion Thus,pachyman in combination with vinorelbine can significantly inhibit the growth of A549 xenografts,and pachyman can regulate the expression of the EGFR gene to increase the efficacy of vinorelbine and cisplatin in lung cancer and decrease the side effects associated with chemotherapy.展开更多
基金support from the National Natural Science Foundation of China(No.81774126,No.81503445 and No.81703919)China Postdoctoral Science Foundation(No.2017M622587)+5 种基金Hunan Provincial Natural Science Foundation(No.2016JJ2095 and No.2017JJ3232)Hunan Provincial Traditional Chinese Medicine Key Research Project(No.201701)Hunan Education Department Scientific Research Project(16C1203 and 16C1216)Hunan Health Department Scientific Research Project(C2015-16,C2016049 and B2016093)Busky Pharmaceutical Collaborative Research Fund,Hunan Provincial Higher Educational Institutions Research Team "Traditional Chinese Medicine prevention and treatment research on infectious diseases" Funding program(No.15)Hunan Province Teaching and Science "Thirteenth Five-Year Plan" Project(No.XJK17BGD057)
文摘Objective To examine the effects of pachyman in combination with vinorelbine and cisplatin on tumor growth and the expression of epidermal growth factor receptor(EGFR)and K-ras in a mouse model of lung cancer induced using the human lung cancer cell line A549,and to investigate the molecular mechanisms underlying the antitumor effects of pachyman.Methods We recorded the size of the tumor xenografts in mice after treatment with pachyman monotherapy or pachymanin combination with vinorelbine and cisplatin.We performed immunohistochemical analysis to determine the levels of expression and distribution of EGFR and K-ras in lung cancer tissues.Real-time fluorescence quantitative PCR was used to determine the relative mRNA expression levels of EGFR and K-ras in lung cancer tissues.Results Vinorelbine and cisplatin significantly decreased the rate of growth of A549 xenografts,and pachyman increased the efficacy of vinorelbine and cisplatin.EGFR and K-ras were widely expressed in A549 xenografts.Vinorelbine and cisplatin could significantly decrease the expression,distribution and mRNA expression levels of EGFR and K-ras in tumor tissues.Pachyman monotherapy significantly decreased the distribution and the mRNA expression levels of EGFR in lung cancer tissues.In addition,pachyman in combination with vinorelbine and cisplatin markedly decreased the distribution and expression levels of EGFR in lung cancer tissues.However,pachyman monotherapy or combination therapy did not significantly decrease the mRNA expression levels of K-ras.Conclusion Thus,pachyman in combination with vinorelbine can significantly inhibit the growth of A549 xenografts,and pachyman can regulate the expression of the EGFR gene to increase the efficacy of vinorelbine and cisplatin in lung cancer and decrease the side effects associated with chemotherapy.