摘要
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AdmIL-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-l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30d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AdmlL,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、AdhlL-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。
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 eytokines interleukin-18 (IL-18) and interleukin-12 (IL-12) were used to induce tumor regression in a C57BIJ6 murine model of prostate cancer (n = 110). Results Adenoviral vectors could express IL-18 and IL-12 effectively. The 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 regress the established tumors, hut 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 immune responses.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2013年第20期1590-1593,共4页
National Medical Journal of China