三氧化二砷誘導SGC7901細胞凋亡及對bcl-2\\cyclin D1表達的影響

[摘要]目的 了解三氧化二砷對胃腺癌SGC7901細胞株細胞增殖、細胞凋亡以及bcl-2、cyclin D1基因表達的影響。方法 分別以不同濃度的三氧化二砷作用于SGC7901細胞，作用不同時間后采用MTT檢測法對細胞增殖活性進行檢測;采用流式細胞儀(FCM)AnnexinV/PI雙染法檢測細胞凋亡率;逆轉錄-聚合酶鏈式反應(RT-PCR)檢測bcl-2、cyclinD1基因轉錄水平。結果 稍高濃度(≥2μmol/L)的三氧化二砷可抑制SGC7901細胞增殖，并有劑量和時間依賴性。逆轉錄聚合酶鏈式反應(RT-PCR)檢測bcl-2、cyclin D1基因轉錄水平，發現三氧化二砷作用組bcl-2、cyclin D1基因的表達與對照組比較明顯減低(P<0.01)。結論 三氧化二砷可有效抑制SGC7901細胞增殖，誘導SGC7901細胞凋亡，與作用劑量和作用時間呈正相關，這一過程可能與三氧化二砷抑制bcl-2、cyclin D1表達有關。

[關鍵詞] 胃腺癌;三氧化二砷;細胞凋亡;bcl-2;cyclin D1

[中圖分類號] R735.2 [文獻標識碼] A [文章編號] 1673-9701(2010)04-32-03

Arsenic Trioxide-induced SGC7901 Cell Apoptosis and Its Effect on Gene Expression of bcl-2 and cyclin D1

HUANG DefengZHAO ZhiguoMA JunCUI Yi

Department of Gastroenterology，the Second Affiliated Hospital of Zhengzhou University，Zhengzhou 450014，China

[Abstract] Objective To investigate the effect of arsenic trioxide on gastric adenocarcinoma cell line SGC7901 cell proliferation，apoptosis，and bcl-2，cyclin D1 gene expression. Methods SGC7901 cells were treated with different concentrations of arsenic trioxide at different time and after that，the proliferation of SGC7901 cells，the apoptosis rate and the gene transcription level of bcl-2 and cyclin D1 were detected by MTT，by flow cytometry and AnnexinV/PI double staining and by RT-PCR，respectively. Results Slightly high concentration of arsenic trioxide(≥2μmol/L) could inhibit cell proliferation and induce SGC-7901 apoptosis， with a dose-and time -dependency. The bcl-2 and cyclin D1 gene expression was obviously lowered in the arsenic trioxide group than that of the control(P<0.01). Conclusion Arsenic trioxide can effectively inhibit cell proliferation and induce SGC7901 apoptosis，with a direct relation to the dose and time，which may be correlated with the inhibition of bcl-2 and cyclin D1 expression by arsenic trioxide.

[Key words] Gastric adenocarcinoma;Arsenic trioxide;Apoptosis;bcl-2;cyclin D1

三氧化二砷(arsenic trioxide，ATO)是中藥砒霜的主要有效成分，近年來研究表明，三氧化二砷除了能治療血液系統疾病，對包括胃癌在內的多種惡性實體瘤也有強大的殺傷作用。胃癌是我國常見的惡性腫瘤，其對放、化療的敏感性均較低，死亡率高，晚期尚缺乏有效的治療手段，尋找新的治療藥物和治療手段乃當務之急。

誘導胃癌細胞凋亡是治療的新思路。三氧化二砷可以誘導惡性腫瘤細胞凋亡進而抑制腫瘤生長發揮治療作用，分子機制涉及多個凋亡調控分子[1]。周期素D1(cyclin D1)能激活CDK2、4、5，促進細胞由G1期進入S期，進行DNA合成，使細胞持續性增殖[2]。bcl-2是從濾泡性淋巴瘤中分離出的一種癌基因，也是細胞凋亡抑制因子，具有抑制細胞凋亡、延長細胞壽命的功能[3]。……