Effect and mechanism of EGFR expression in macrophaegs on the anti-cancer ef ect ofb erberine on colorectal cancer
10.3760/cma.j.issn.0253-3766.2015.05.005
- VernacularTitle:巨噬细胞表皮生长因子受体表达对小檗碱抗结直肠癌作用的影响及机制
- Author:
Ning LU
1
;
Zhongsheng TONG
;
Mei ZHANG
;
Lu LU
;
Hailong CAO
Author Information
1. 300060天津医科大学肿瘤医院肿瘤内科,国家肿瘤临床医学研究中心 天津市肿瘤防治重点实验室
- Keywords:
Colorectal neoplasms;
Berberine;
Macrophages;
Receptor,epidermal growth factor;
Cell proliferation;
Apoptosis;
Mice
- From:
Chinese Journal of Oncology
2015;(5):342-346
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and explore its possible mechanisms of epidermal growth factor receptor(EGFR) expression in macrophages on the anti-cancer effect of berberine (BER) on the growth of colorectal cancer.Methods Mice with EGFR gene defects in macrophages ( Egfrfl/fl LysM-Cre) and with EGFR gene expression in macrophages ( LysM-Cre ) ( control group ) were treated with azoxymethane ( AOM ) to establish colorectal tumor models.These models were treated with or without berberine ( BER) intervention.The number of colorectal tumors and the gut length in the two groups were measured.The proliferation of tumor cells was detected by Ki-67 immunohistochemistry and apoptosis was detected by annexin V-FITC fluorescence labeling.Western blot was used to detect the expression of cleaved-caspase-3 protein.Results After treated with AOM, the colorectal tumor number was 10.26±1.43 in the LysM-Cre group and7 .62±1.05 in the Egfrfl/fl LysM-Cre group, showing a significant difference ( P=0.021) . The gut length was (6.04±1.06) cm in the LysM-Cre group and (6.39±0.92) cm in the gfrfl/flLysMC-re group, with a non-significant difference between the two groups ( P=00.75 ) .After treated with AOM plus BER intervention,the colorectal tumor number of the LysM -Cre group was 8.35±1.22 and that in the Egfrfl/fl LysM-Cre group was 2.66±0.38, showing a very significant difference between the two groups ( P=0.006) . The gut length of the LysM-Cre group was ( 7.34 ±1.16) cm and that of the Egfrfl/fl LysM-Cre group was (10 .01±1.72) cm ( P=0.028) .After treated with AOM, the ratio of Ki-67-positive tumor cells in the LysM-Cre group was (78.31±3.43)%and that in the Egfrfl/flLysM-Cre group was (75.85±2.92)%(P=0.282). After AOM plus BER treatment, the ratio of Ki-67-positive tumor cells in the LysM-Cre group was (42.43± 3.09)%and that in the Egfrfl/flLysM-Cre group was significantly lower (29.65±2.47)%(P=0.018).The ratio of annexin V-positive tumor cells was (0.95±0.13)%in the LysM-Cre group, not significantly different from (1.13±0.16)%in the Egfrfl/flLysM-Cre group (P=0.175).After AOM plus BER treatment, the ratio of annexin V-positive tumor cells in the LysM-Cre group was (32.10±1.97)%, significantly lower than the (47.08 ±2.83)% in the Egfrfl/fl LysM-Cre group ( P=0.010).The level of cleaved-caspase-3 protein expression was 235.92±19.73 in the Egfrfl/flLysM-Cre group, significantly higher than the 119.71±12.87 in the LysM-Cre group ( P=0.012 ) .Conclusions The growth of colorectal cancer cells in mice can be inhibited by BER treatment, and this anti-cancer effect of BER can be further enhanced by EGFR gene knockout in macrophages.The mechanisms may be related to the inhibition of proliferation and promotion of apoptosis in colorectal cancer cells.
