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作 者:申咏梅[1] 杨晓春[1] 石怡珍[1] 谢小芳[2] 唐军[1]
机构地区:[1]苏州大学附属第二医院放免中心,江苏苏州215004 [2]苏州大学附属第二医院检验教研室,江苏苏州215004
出 处:《细胞与分子免疫学杂志》2007年第8期727-730,共4页Chinese Journal of Cellular and Molecular Immunology
基 金:国家自然科学基金资助项目(30400111);江苏省自然科学基金资助项目(BK2004041)
摘 要:目的:研究bcl-2硫代反义寡核苷酸(bcl-2 ASODN)联合Rituximab[CD20单克隆抗体(mAb)]对B细胞淋巴瘤Raji细胞株体内外增殖和凋亡的影响, 并探讨其作用机制.方法:bcl-2 ASODN和Rituximab分别和联合作用B细胞淋巴瘤Raji细胞后, 通过MTT法检测细胞生长情况;流式细胞术(FCM)检测bcl-2蛋白表达和细胞凋亡;RT-PCR检测bcl-2 mRNA表达水平;用Raji细胞建立裸鼠B细胞淋巴瘤模型观察bcl-2 ASODN与Rituximab联合在体内的抗肿瘤效果. 结果:5~30 μmol/L bcl-2 和1 ~16 mg/L Rituximab单独应用均能抑制Raji细胞生长、诱导细胞凋亡、使bcl-2蛋白和bcl-2 mRNA表达降低, 但两者联合应用较单独应用抑制作用更为明显(P<0.01).体内实验表明, bcl-2 ASODN与Rituximab联合应用较单独可有效抑制BALB/c裸鼠B细胞淋巴瘤的生长(P<0.01).结论:bcl-2 ASODN联合Rituximab较分别单独应用可明显抑制B细胞淋巴瘤Raji细胞生长, 促进细胞凋亡;其机制可能是通过联合下调bcl-2蛋白及bcl-2 mRNA表达而起作用.AIM: To study the combinational effects of bcl-2 antisense oligodeoxynucleotide (bcl-2 ASODN ) and Rituximab (anti-CD20 monoclonal antibody) on proliferation and apoptosis of B-lymphoma Raji cells in vitro and in vivo, and to explore the possible mechanisms. METHODS : After bcl-2 ASODN and Rituximab treating on Raji cells respectively or cooperatively, the proliferation of Raji cells, the expression of bcl-2 protein, the apoptosis and the expression of bcl-2 mRNA were detected by MrT assay, flow cytometry (FCM) and RT-PCR, respectively. The combinational antitumor activity of bcl-2 ASODN and Rituximab was evaluated in BALB/c nude mice bearing B-lymphoma inoculated with Raji cells. RESULTS: 5 -30 μmol/L bcl-2 ASODN and 1 - 16 mg/L Rituximab could inhibit Raji cells' growth, induce apoptosis and decrease the expression of bcl-2 protein and bcl-2 mRNA alone. But there was much more effective inhi- bition of growth and induction of apoptosis by their combination than alone ( P 〈 0.01 ). In tumor bearing mice, combination of bcl-2 ASODN and Rituximab showed a significant inhibitory effect on the growth of transplanted B-lymphoma, resulting in a statistically significant difference compared with alone (P 〈 0.01 ). CONCLUSION: It has been found that bcl-2 ASODN combined with Rituximab could significantly inhibit the growth of Raji cells and induce their apoptosis via reinforcing specific down regulation of bcl-2 protein and bcl-2 mRNA expression.
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