Expression and its significance of methyl CpG binding protein 2 in gastric cancer / 中华消化杂志

ABSTRACT

Objective To explore the expression of methyl CpG binding protein 2 (MeCP2) in gastric cancer tissues and its role in multi-drug resistance (MDR) in gastric cancer cells.Methods The expression of MeCP2 in 90 gastric cancer tissues and the adjacent normal tissues was detected by immunohistochemistry,and the relationship between MeCP2 expression level and clinicopathological parameters was analyzed.The expression level of MeCP2 in gastric cancer cell line SGC7901,MDR cell variants SGC7901/doxorubicin hydrochloride(ADR) and SGC7901/vincristine(VCR)was determined by Western blot.After the expression of MeCP2 was silenced by short interference RNA (siRNA),half inhibitory concentration (IC50) of 5-fluorouraeil and cisplatin in gastric cancer cell was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide(MTT) assay.The t test or chi square test was performed for statistical analysis.Results The positive rate of MeCP2 expression in gastric cancer tissues was 72.2％ (65/90),which was significantly lower than that in adjacent normal tissues (93.3％,84/ 90),and the difference was statistically significant (x2 =14.068,P＜0.01).MeCP2 expression was not correlated with age,tumor maximum diameter and lymph node metastasis (all P＞0.05),however which was related to gender,clinical TNM stages and distant metastasis (x2=4.680,4.186 and 4.327;aH P＜ 0.05).The gray scale ratios of MeCP2/β-actin in SGC7901/ADR and SGC7901/VCR were 0.593 7 ± 0.030 5 and 0.651 2 ± 0.018 6,which were lower than that of parental SGC7901 cells (1),and the differences were statistically significant (t =23.080,17.360;both P ＜ 0.01).After the expression of MeCP2 was silenced by siRNA,the IC50 of 5-fluorouracil and cisplatin in SGC7901 transfected with MeCP2 specific siRNA were (11.540 0±0.469 3) μg/mL and (2.273 0±0.265 4) μg/mL,which were higher than the IC50 of 5-fluorouracil and cisplatin in SGC7901 transfected with non-related oligonucleotide sequence ((8.663 0±0.160 1) μg/mL and (0.884 0 ±0.038 6) μg/mL),respectively.The differences were statistically significant (t =15.380 and 8.153;both P ＜ 0.01).Conclusions The expression of MeCP2 in gastric cancer tissues significantly decreased,which was correlated with clinical stages,distant metastasis.MeCP2 can inhibit the MDR of gastric cancer cell,which indicated the dysregulated expression of MeCP2 might participate in the genesis and development of gastric cancer.