重组腺病毒介导白细胞介素18、12联合基因治疗前列腺癌的实验观察
Adenovirus-mediated combined gene therapy of interleukin-18 and interleukin-12 for prostate cancer: an experimental study
目的 探讨晚期前列腺癌的治疗方法,为前列腺癌免疫基因治疗提供实验性依据.方法 采用重组腺病毒介导白细胞介素(IL)-18、IL-12联合免疫基因疗法,对110只C57BL/6小鼠前列腺癌模型进行致瘤性和抑瘤性观察.结果 腺病毒Adm IL-18、AdhIL-12能有效表达目的基因.接种野生型、转AdLacZ、转AdmIL-18的RM-1细胞、转AdhIL-12的RM-1细胞、转AdmIL-18、AdhIL-12混合RM-1细胞的小鼠致瘤比例分别为10/10、10/10、4/10、5/10及2/10;成瘤时间分别为(12.3±1.5)、(12.8±1.0)、(15.4±1.3)、(14.8±0.8)、(24.5±2.2)d;接种30 d后肿瘤结节直径分别为(37.0±3.0)、(35.0±4.6)、(25.0±2.0)、(27.0±4.1)及(9.5±3.2)mm.与其他4组比较,转AdmIL-18、AdhIL-12基因RM-1细胞小鼠致瘤率下降,成瘤时间延迟(P<0.01)、瘤结节小(P<0.01).AdmIL-18、AdhIL-12瘤体注射还可抑制肿瘤生长(P<0.01),减少肺转移灶数目(P<0.01).结论 IL-18、IL-12联合基因治疗可诱发前列腺癌小鼠的肿瘤特异性免疫反应.
更多Objective To explore the therapeutic regimens of metastatic prostate cancer so as to provide the experimental rationales for its gene therapy.Methods The adenoviral vectors expressing cytokines interleukin-18 (IL-18) and interleukin-12 (IL-12) were used to induce tumor regrcssion in a C57BI/6 murine model of prostate cancer (n =110).Results Adenoviral vectors could express IL-18 and IL-12 effectivcly.Thc rates of tumorigenesis were 10/10,10/10,4/10,5/10 and 2/10,the durations of tumor growth (12.3 ±1.5),(12.8 ±1.0),(15.4 ±1.3),(14.8 ±0.8),(24.5 ±2.2) days and the diameters of tumor nodule after inoculation 30 days (37.0 ±3.0),(35.0 ±4.6),(25.0 ±2.0),(27.0 ± 4.1) and (9.5 ± 3.2) mm respectively in inoculation wild-type,AdLacZ,AdmIL-18,AdhIL-12,AdmIL-18 and AdhIL-12 of RM-1 cell.Compared to the other four groups,AdmIL-18 and AdhIL-12 developed smaller and delayed tumors (P < 0.01).Intratumoral injection of Adm IL-18 and AdhIL-12 could not only rcgress thc cstablished tumors,but also reduce the number of distal lung metastases (P < 0.01).Conclusion Adenovirus-mediated delivery of IL-18 and IL-12 locally by intratumoral injection is highly effective in inducing specific antitumor immunc responscs.
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