Effects of Pachyman in Combination with Vinorelbine and Cisplatin on Tumor Growth and the Expression of EGFR and K-ras in Mice with Lung Cancer

Abstract

ABSTRACT: 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. Keywords: Pachyman, Vinorelbine, Cisplatin, Lung cancer, EGFR, K-ras