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目的:探讨RNA干扰抑制DNMT基因对小鼠肿瘤体积和原癌基因表达的影响。方法:将30只胰腺癌模型裸鼠平均分为空白组、对照组与实验组,空白组腹腔注射普通细胞培养液50 mg·kg-1,对照组腹腔注射转染空载体细胞培养悬浮液50 mg·kg-1,实验组腹腔注射转染RNA干扰DNMT1 siRNA载体细胞培养悬浮液50 mg·kg-1,均连续注射15 d。结果:胰腺癌模型裸鼠的肿瘤结节明显、瘤体不规则、没有破溃与坏死,肿瘤生物学特性稳定。实验组肿瘤生长曲线平缓,但未停滞;空白组与对照组肿瘤生长较快,曲线陡直,处理后各组体积比较差异有统计学意义(P<0.05)。3组处理前的裸鼠体质量差异无统计学意义,处理后实验组的体质量明显低于其他两组;同时处理处死后实验组的瘤质量也明显低于其他两组,实验组肿瘤生长明显受抑制,差异均有统计学意义(P<0.05)。处理后空白组与对照组的肿瘤表面血管丰富,色泽红润;实验组的肿瘤体积明显缩小,表面浅黄色,未见肿瘤转移灶,可见部分细胞核固缩、裂解,出现凋亡。免疫组化分析结果显示处理后实验组的AFP与Ki-67的相对表达量均明显低于对照组与空白组(P<0.05)。结论:RNA干扰抑制DNMT基因在裸鼠肿瘤的应用能抑制原癌基因表达,抑制肿瘤体积与体质量的增加,从而有利于发挥抗肿瘤作用。
Objective: To investigate the effect of RNA interference on DNMT gene expression on tumor volume and proto-oncogene in mice. Methods: Thirty pancreatic cancer model nude mice were equally divided into blank group, control group and experimental group. The blank group was injected intraperitoneally with 50 mg · kg-1 normal cell culture medium and the control group was injected intraperitoneally with empty vector to culture suspension 50 mg · kg-1. The experimental group was intraperitoneally injected with RNA interference DNMT1 siRNA carrier cell culture suspension 50 mg · kg-1, were injected 15 consecutive days. Results: The tumor nodules of pancreatic cancer model nude mice were obvious, the tumor was irregular, there was no rupture and necrosis, and the tumor biological characteristics were stable. The tumor growth curve of the experimental group was flat but not stagnated. The tumor growth of the blank group and the control group was rapid and the curve was steep. The volume of each group after treatment was significantly different (P <0.05). The body weight of nude mice before treatment was no significant difference among the three groups. After treatment, the body weight of experimental group was significantly lower than that of the other two groups. At the same time, the tumor mass of experimental group after treatment was also significantly lower than that of the other two groups. Obviously inhibited, the differences were statistically significant (P <0.05). After treatment, the tumor surface of the blank group and the control group were rich in blood vessels and had a ruddy color. The tumor volume of the experimental group was significantly reduced, the surface was yellowish, and no metastasis was seen. Some nuclei were pyknotic, lysed and apoptotic. The results of immunohistochemistry showed that the relative expression of AFP and Ki-67 in the experimental group was significantly lower than that in the control group and the blank group (P <0.05). Conclusion: Inhibition of DNMT gene by RNAi in nude mice can inhibit the expression of proto-oncogene and inhibit the increase of tumor volume and body weight, which is beneficial to the anti-tumor effect.