转染人乳头瘤病毒的宫颈癌U14移植同系小鼠后的生长特性和转移规律

目的 :探讨转染人乳头瘤病毒 (HPV)的小鼠宫颈癌U1 4移植同系小鼠后生长特性和转移规律。方法 :用电穿孔法及阳离子脂质体将HPV 1 6型的早期基因E6 ,E7分别转染小鼠宫颈癌U1 4,筛选、鉴定表达E6 ,E7的转化细胞即E6 +U1 4,E7+U1 4,然后分别经皮下和腹腔移植于同系小鼠 ,观察其生长特性和转移规律。结果 :皮下移植野生型U1 4,E6 +U1 4及E7+U1 4后 ,出瘤时间分别为 5～ 7d ,1 1～ 1 4d及 8～ 1 0d (P <0 .0 5 ) ;平均生存期分别为 2 9d ,43 .3d及 3 5d ;淋巴转移率分别为 90 % ,3 0 %及 40 % ;肺转移率分别为 6 0 % ,1 0 %及 2 0 %。腹腔内移植后 ,荷瘤小鼠平均寿命分别为 1 4.2d ,2 0 .6d及 1 8.3d ;未发现淋巴和肺转移。结论 :转染HPV的小鼠宫颈癌U1 4移植同系小鼠后 ,显示出与移植野生型不同的生长特性和转移规律。该模型为研究以HPVE6 ,E7为靶的免疫或其他方法治疗宫颈癌提供了有价值的动物模型。

Growth behavior and metastatic pattern of cervical cancer U14 transfected with human papillomavirus in inbred mouse

Objective To investigate the growth behavior and metastatic pattern of murine cervix cancer U14 transfected with human papillomavirus(HPV) in inbred 615 strain mouse. Methods We transfected HPV 16 E6 and E7 genes into mouse cervix carcinoma cell strain NO. 14 (U14) by electroporation and liposome, respectively. The transfectants were selected by G418 , and several high expressed HPV16 E6 and E7 clonal cell lines (E6 +U14, E7 +U14) were detected by PCR and by immunohistochemistry. We transplanted those cells into inbred 615 strain mice both subcutaneously and intraperitoneally to observe the growth behavior and metastasis of them. Results The durations of tumor appearance were 5～7 d, 11～14 d, and 8～10 d after having been transplanted subcutaneously with wild type U14, E6 +U14, and E7 +U14, respectively(P<0.05). The mean survival times of mice were 29 d, 43 d, and 35 d, respectively . Metastasis could be found both in lymph nodes (90%, 30%, and 40%, respectively) and lungs (60%, 10%, and 20%, respectively). After intraperitoneal inoculation, the mean survival durations of mice were 14. 2 d,20. 6 d and 18. 3 d. We could not find metastasis both in lymph nodes and lungs. Conclusion Murine cervix cancer U14 cells transfected with HPV16 E6 and E7 have different growth behavior and metastatic patterns after transplanted in inbred mice, which provide useful models for studying their immunotherapy or other strategies for cervical cancer with E6 and E7 as a target.