Department of Oncology, The First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, P.R. China.
Oncol Rep. 2010 Mar;23(3):693-700. doi: 10.3892/or_00000686.
Cimetidine, a histamine-2 (H2) receptor antagonist, has been demonstrated to have anticancer effects on various types of malignancies. However, the mechanisms of its action on gastric cancer are not completely understood. This study was designed to investigate its antitumor effect and underlying mechanisms in human gastric cancer SGC-7901 and MGC-803 cells. The MTT assay was used to evaluate cell viability, and flow cytometry, acridine orange staining and transmission electron microscopy were used to detect apoptosis, for cultured cells. The protein expression in cells was evaluated by Western blot analysis and colorimetric assay. Gastric tumors were established by subcutaneous injection of SGC-7901 cells in nude BALB/c mice, and cimetidine was administered to the mice. The size of tumors was monitored and the weight of tumors was examined. The exposure of gastric cancer cells to cimetidine resulted in growth inhibition and the induction of apoptosis in a dose-dependent manner. Activation of the caspase cascade for both the extrinsic and intrinsic pathways were demonstrated in vitro, including caspase-8, -9 and -3. We also found that the expression of Bcl-2 protein decreased and the expression of Bax protein increased which lead to an increase of the Bax/Bcl-2 ratio. In mice bearing SGC-7901 xenograft tumors, administration of cimetidine showed a significant decrease of tumor volumes and tumor weight compared with the control. Our results showed that cimetidine exhibited antitumor effects in gastric cancer cells with an induction of apoptosis.
西咪替丁是一种组胺 2（H2）受体拮抗剂，已被证明对多种恶性肿瘤具有抗癌作用。然而，其在胃癌中的作用机制尚不完全清楚。本研究旨在探讨西咪替丁对人胃癌 SGC-7901 和 MGC-803 细胞的抗肿瘤作用及其机制。MTT 法检测细胞活力，吖啶橙染色和透射电镜观察细胞凋亡，Western blot 分析和比色法检测细胞内蛋白表达。将 SGC-7901 细胞皮下注射裸鼠建立胃癌肿瘤模型，给予西咪替丁治疗，监测肿瘤大小并检测肿瘤重量。西咪替丁处理胃癌细胞可抑制其生长并诱导其凋亡，呈剂量依赖性。体外实验证明了外源性和内源性途径 caspase 级联的激活，包括 caspase-8、-9 和 -3。我们还发现 Bcl-2 蛋白表达减少，Bax 蛋白表达增加，导致 Bax/Bcl-2 比值增加。在 SGC-7901 移植瘤裸鼠模型中，与对照组相比，西咪替丁给药可显著降低肿瘤体积和肿瘤重量。我们的结果表明，西咪替丁在胃癌细胞中具有诱导细胞凋亡的抗肿瘤作用。
