1. Antitumor activity of taspine by modulating the EGFR signaling pathway of Erk1/2 and Akt in vitro and in vivo
- Author
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Yanmin Zhang, Yinnan Chen, Langchong He, Lei Zheng, Bingling Dai, Nan Wang, and Jie Zhang
- Subjects
MAPK/ERK pathway ,Cell signaling ,MAP Kinase Signaling System ,Pharmaceutical Science ,Down-Regulation ,Mice, Nude ,Analytical Chemistry ,Cell Line ,chemistry.chemical_compound ,Mice ,Random Allocation ,Alkaloids ,Epidermal growth factor ,Cell Movement ,Drug Discovery ,Animals ,Humans ,Protein kinase B ,EGFR inhibitors ,Cell Proliferation ,Pharmacology ,Mice, Inbred BALB C ,Dose-Response Relationship, Drug ,Epidermal Growth Factor ,Organic Chemistry ,Taspine ,Berberidaceae ,Antineoplastic Agents, Phytogenic ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,Complementary and alternative medicine ,chemistry ,Cancer research ,Molecular Medicine ,Phosphorylation ,Female ,Signal transduction ,Proto-Oncogene Proteins c-akt ,hormones, hormone substitutes, and hormone antagonists ,Rhizome ,Drugs, Chinese Herbal - Abstract
EGFR, as a critical signaling pathway in many human tumors, has become an important target of cancer drug design. Taspine has shown meaningful angiogenesis activity in previous studies. This paper is to investigate the antitumor action of taspine by modulating the EGFR signaling pathway. The study determined the expression of key signaling molecules of EGFR (EGFR, Akt, p-Akt, Erk, and p-Erk) by Western blot and real-time PCR and analyzed their correlations with subsequent reactions. In addition, the cell proliferation, migration, and EGF production were examined by MTT, transwell system, and ELISA. The antitumor activity in vivo was carried out by xenograft in athymic mice. The results showed that taspine could inhibit A431 and Hek293/EGFR cell proliferation and A431 cell migration as well as EGF production. Compared to the negative control, EGFR, Akt, and phosphorylation of Akt were significantly inhibited by taspine treatment in A431 and HEK293/EGFR cells. Consistent with the inhibition of Akt activity, Erk1/2 and its phosphorylation were reduced. Moreover, taspine inhibited A431 xenograft tumor growth. These results suggest that EGFR activated by EGF and its downstream signaling pathways proteins could be downregulated by taspine in a dose-dependent manner. The antitumor mechanism of taspine through the EGFR pathway lies in the ability to inhibit A431 cell proliferation and migration by reducing EGF secretion. This occurs through the repression of EGFR which mediates not only MAPK (Erk1/2) but also Akt signals.
- Published
- 2011