摘要
目的检测2株胃癌细胞是否可作为17β-雌二醇(E2)及其拮抗剂三苯氧胺(TAM)作用的靶细胞;检测E2及TAM对胃癌细胞胸腺素α原(ProTα)mRNA表达的影响,探讨TAM在胃癌治疗中的作用。方法首先,RT-PCR和免疫细胞化学(ICC)法检测胃癌细胞SGC-7901和BGC-823的雌激素受体(ER)亚型ERα和ERβ的表达。随后,分别观察不同浓度的E2和TAM对细胞生长速度和细胞形态学的影响。用噻唑蓝(MTT)比色法测定细胞存活率,Hoechst 33258染色(法)检测细胞凋亡。再用半定量RT-PCR检测不同浓度的E2和TAM对BGC-823细胞ProTα基因表达的影响。结果 (1)ERα在SGC-7901细胞有阳性表达。在BGC-823细胞,ERα和ERβ均有表达。(2)10 nmol/L E2可促进2株胃癌细胞的生长,且增殖的BGC-823细胞伴有ProTαmRNA水平增高(P<0.05)。(3)TAM对SGC-7901和BGC-823有生长抑制及诱导凋亡作用(P<0.05),同时伴有ERα(+)/ERβ(+)BGC-823细胞ProTαmRNA表达水平下降(P<0.05)。结论 E2和TAM能够影响ERα和ERβ阳性胃癌细胞生长。SGC-7901和BGC-823的生长具有E2依赖性,可能与其ERα阳性特征有关。E2和TAM能够通过ProTα直接或间接作用影响ERα(+)/ERβ(+)胃癌细胞生长。抗E2治疗对某些胃癌可能有效。
Objective To demonstrate gastric cancer cells as targets for receptor-mediated estrogenic and antiestrogenic action and to evaluate the potential of using antiestrogens as gastric cancer therapies.Methods We have analyzed whether transcripts of ERα and ERβ were expressed in two gastric cancer cell lines established from Chinese with gastric adenocarcinoma(SGC-7901 and BGC-823) by RT-PCR and ICC.In the two gastric cancer cell lines,SGC-7901 expressed ERα alone and BGC-823 cells expressed ERα and ERβ.The ERβ expression was at a lower level than ERα in BGC-823 cell line and the level of ERs expression was lower than that observed in breast carcinoma cell line MCF-7.To evaluate the potential of using antiestrogens as gastric cancer therapies,we have assessed the growth-inhibitory action of estrogen(estradiol,E2) and antiestrogen(tamoxifen,TAM) on these cultures.MTT assay and Hoechst 33258 staining were used to detect cytotoxicity and apoptosis.Recently,ProTα has also shown are one of estradiol-response genes in some cells.Whether there is a possible relationship of ProTα to ERs in gastric carcinogenesis is unknown.To investigate the possible mechanism of E2 and TAM in human gastric cancer,the effects of E2 and TAM on ProTα mRNA regulation in BGC-823 cell were estimated by RT-PCR.Results E2 induced proliferation in both cell lines(P<0.05).Unlike the MCF-7 cells,which responded to the low concentration(1 nmol/L),the treated SGC-7901 and BGC-823 cells have mainly been affected at a higher dose(10 nmol/L) at which a significant increase was also obtained on the ProTα mRNA level in BGC-823(P<0.05).TAM had growth-inhibitory effects and induced apoptosis in both cell lines(P<0.05).Interestingly,BGC-823 displayed an increased apoptosis at a lower dose(1 μmol/L) of TAM than SGC-7901(10 μmol/L).On the other hand,10 μmol/L TAM had growth-inhibitory effects and induced apoptosis with effectively decreased the expression of ProTα mRNA of BGC-823 cells(P<0.05).Conclusions Our results suggested that estrogen signalin
出处
《中华临床医师杂志(电子版)》
CAS
2011年第14期4133-4140,共8页
Chinese Journal of Clinicians(Electronic Edition)
基金
辽宁省教育厅高等学校科研项目(2009S028)
关键词
胃肿瘤
雌激素受体Α
雌激素受体Β
胸腺素Α原
Stomach neoplasms
Estrogen receptor alpha
Estrogen receptor beta
Prothymosin alpha