赫赛汀和9-顺式视黄酸联合用药对裸鼠转染HER2基因乳腺癌效应的研究

目的探讨赫赛汀(Herceptin,HER)和9-顺式视黄酸(9-cis-RA)单独和联合用药对HER2阳性乳腺癌细胞裸鼠移植瘤的协同抑制效应及其相应机制。方法将处于对数生长期的MCF-7HER2细胞皮下注射到Balb/c裸鼠体内,4w后,HER和9-cis-RA分别单独和联合处理裸鼠移植瘤模型3w,测量各组移植瘤的体积大小并计算出相应的q值。同时观察移植瘤的组织结构,并利用免疫组化法检测移植瘤细胞Ki-67蛋白的表达变化,以检测移植瘤细胞的增殖活性。结果HER和9-cis-RA联合作用组较对照和单独作用组能显著减小HER2阳性乳腺癌细胞裸鼠移植瘤的体积并有效改变其组织病理结构,同时还能在体内显著抑制HER2阳性乳腺癌细胞的增殖活性。结论联合应用HER和9-cis-RA可在体内有效协同发挥抑制HER2阳性乳腺癌细胞的作用。

THE SYNERGISTIC EFFECTS OF HERCEPTIN AND 9-CIS-RETINOIC ACID ON HER2/NEU POSITIVE BREAST CANCER CELLS IN VIVO

Objective To observe the synergistic effects of Herceptin(HER)and 9-cis-retinoic acid (9-cis-RA) on HER2/neu positive breast cancer cells in vivo. Method MCF-7 breast cancer cells transfected with exogenous HER2 gene were inoculated into athymic nude mice. Four weeks after tumor inoculation,mice bearing a tumor of 200 mm3 in volume approximately were selected to be treated with HER and/or 9-cis-RA(SC) for 20d. After that tumor volume was precisely measured,concurrently the HE staining and Ki-67 immunohistochemical (IHC) assay were performed to detect the anti-proliferative effect of HER in combination with 9-cis-RA in vivo. Results After 3 w of treatment,HER and 9-cis-RA synergistically decreased the tumor volume as compared with control group. IHC results showed that Ki-67 expression was significantly inhibited by co-treatment of HER and 9-cis-RA,which means the arrest of cell cycle progression. Conclusion Herceptin and 9-cis-RA could synergistically inhibit the proliferation of HER2 positive breast cancer cells in vivo.