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05 February 2018 : Animal Research  

Protein Kinases Type II (PKG II) Combined with L-Arginine Significantly Ameliorated Xenograft Tumor Development: Is L-Arginine a Potential Alternative in PKG II Activation?

Yan Wu12AEG, Ying Liu1B, Zhensheng Cai1B, Huijuan Qin1C, Hongfan Li1B, Wenbin Su1C, Ying Wang1B, Hai Qian1C, Lu Jiang1A, Min Wu1F, Ji Pang1A, Yongchang Chen1AEG

DOI: 10.12659/MSM.906213

Med Sci Monit 2018; 24: ANS736-742

Abstract

BACKGROUND: The mammalian cyclic guanosine monophosphate (cGMP)-dependent protein kinases type II (PKG II) plays critical physiological or pathological functions in different tissues. However, the biological effects of PKG II are dependent on cGMP. Published data indicated that L-arginine (L-Arg) promoted NO production, NO can activate soluble guanylate cyclase (sGC), and catalyzes guanosine triphosphate (GTP) into cGMP, which suggested L-Arg could activate PKG II. Therefore, the present work was performed to address: (i) whether L-Arg could be a potential alternative in PKG II activation, and (ii) whether L-Arg also contributes to PKG II against cancer.

MATERIAL AND METHODS: Nude BALB/c mice were inoculated with human MCF-7, HepG2, and SW480 cell lines via subcutaneous (s.c.) injecting. After 7 days of inoculation, Ad-PKG II was injected into the cancer tissues every 4 days, and the next day 10 μmol/mouse L-Arg was administered. Western blotting and immunohistochemistry were used to assess protein expression.

RESULTS: Our results demonstrated that L-Arg significantly activated PKG II and effectively ameliorated xenograft tumor development through inhibiting cancer growth, angiogenesis, and metastasis, which was partially dependent on blocking of epidermal growth factor receptor (EGFR) activity, as well as downstream signaling pathways such as Erk1/2.

CONCLUSIONS: Our results provide an exciting new insight: L-Arg is a potential alternative to PKG II activation.

Keywords: Arginine, Colorectal Neoplasms, Hereditary Nonpolyposis, Vascular Endothelial Growth Factor, Endocrine-Gland-Derived

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750