CRF2 Receptors

Epidermal growth factor receptor (EGFR) plays an essential role in human nonCsmall cell lung cancer (NSCLC) tumorigenesis

Epidermal growth factor receptor (EGFR) plays an essential role in human nonCsmall cell lung cancer (NSCLC) tumorigenesis. xenograft mouse model. Thus, oxymatrine appears to be a novel therapeutic agent for NSCLC treatment. and tumor growth The animal study was approved by the Animal Ethics Committee Dexrazoxane HCl of Central South University. HCC827 cells (1??106/100?tumor growth We further determined the antitumor effects of oxymatrine on NSCLC cells in a xenograft mouse model. HCC827 cells were transplanted into the right flank of 6\week\old female athymic nude mice. Oxymatrine (50?mg/kg per day) or vehicle treatment was initiated when the average tumor volume reached 50?mm3. Results indicated that the final average tumor volume of the vehicle\treated group was around 752.02??146.76?mm3, whereas average tumor size of the oxymatrine\treated group was 479.92??91.89?mm3 (Fig.?6A and B). The Dexrazoxane HCl average tumor weights of the vehicle\treated group and oxymatrine\treated group were 0.77??0.08?g and 0.47??0.05?g, respectively (Fig.?6C). During the treatment period, oxymatrine did not affect body weight of the mice (Fig.?6D). IHC analysis showed Dexrazoxane HCl that oxymatrine substantially inhibited the phosphorylation of EGFR in HCC827 xenograft tumors. Moreover, the protein level of Ki67 was decreased in oxymatrine\treated group (Fig.?6E). Our results indicate that oxymatrine inhibits tumor growth data showed that the consumption of oxymatrine did not induce significant body weight loss occurred in the oxymatrine\treated group (Fig.?6). These results suggested that oxymatrine inhibited NSCLC via targeting EGFR signaling but has no obvious cytotoxicity on normal cells. Recently, Liu et?al. found that oxymatrine synergistically enhances the antitumor activity of oxaliplatin in colon carcinoma 36 and enhances the inhibitory effect of 5\fluorouracil on hepatocellular carcinoma and oncogene product may contribute to cyclin D1 expression 40. Evidence from laboratory investigation discovered that inhibition of EGFR activity by TKIs dramatically suppressed the expression of cyclin D1 protein 41, 42, 43 in NSCLC. Here, we found that oxymatrine\mediated cyclin D1 downregulation was dependent on the suppression of EGFR\Akt signaling, exogenous overexpression of Myr\Akt rescued cyclin D1 expression in the oxymatrine\treated group (Figs.?4 and ?and5).5). However, inhibition of ERK1/2 had no obvious effect on cyclin D1 expression (Fig.?5A). Moreover, recent studies indicated that EGFR can translocate Dexrazoxane HCl to the nucleus and act as a transcription factor or kinase in human cancers 44, 45, 46. The anticancer treatment, such as radiation and Dexrazoxane HCl EGFR\targeted therapy, or other stimuli, including ligand binding, substantially induced EGFR nuclear localization 46, 47. The nuclear EGFR regulates gene expression, such as promotes cyclin D1 transcription 48, 49. Although our results showed that oxymatrine\induced cyclin D1 downregulation was reliant on EGFR\Akt kinases activity partially, there continues to be a chance that oxymatrine straight inhibited EGFR nuclear translocation and EGFR\mediated cyclin D1 transcription regulation. Overall, our data implied that suppression of EGFR signaling pathway is usually involved in oxymatrine\induced tumor inhibition in NSCLC. We analyzed the suppression effect of oxymatrine against WT EGFR, exon 19 deletion and the L858R/T790M mutated EGFR em in vitro /em . For the first time, we identified that decreases the activity of the EGFR\Akt\cyclin D1 signaling pathway was one of the main underlying systems for oxymatrine\induced cell routine arrest in individual NSCLC. Conflicts appealing No potential Rabbit Polyclonal to HSF2 issues of interest had been disclosed. Notes Cancers Medication 2018; 7(1):208C218 [PMC free of charge content] [PubMed].