Chen Qiang, Cui Xiao-Xu, Liang Pei-Fen, Dou Jin-Xia, Liu Zi-Yan, Sun Wen-Wen
Department of Tradition Chinese Medicine, Tianjin 4th Centre Hospital 1# Zhongshan Road, Tianjin 300140, China.
Centre Lab, Tianjin 4th Centre Hospital 1# Zhongshan Road, Tianjin 300140, China.
Am J Transl Res. 2016 Jul 15;8(7):2947-55. eCollection 2016.
To compare the effects and safety of immunotherapy using different methods to load DC-CIK cells for MDA-MB-231 breast cancer stem cells.
A breast cancer model was established in BALB/c nude mice using breast cancer stem cells. All mice were randomly divided into six groups, and each group had three nude mice: the blank control group, the DC-CIK group (group D), the MDA-MB-231 CSC whole-cell lysate DC-CIK group (group L-D), the MDA-MB-231 CSC RNA DC-CIK group (group R-D), the THP DC-CIK group (group T-D) and group THP. Nude mice in groups D, L-D, R-D and T-D were injected with CSCs; 4 days later, the mice were inoculated with 1 × 10(6) DC-CIK cells via the tail vein. This injection was repeated 2 times a week for three weeks. The mice in groups THP and T-D were injected with a 5 mg/Kg dose of THP chemotherapeutic agents via the tail vein the day before DC-CIK injection, which was repeated one time a week for three weeks. Nude mice in the blank control group were injected with normal saline. The weights and sizes of the tumors were measured after the mice were euthanized. The expression of c-Myc, a key proto-oncogene associated with the Akt signaling pathway, was detected with RT-PCR.
The tumor growth rates in each group were as follows: group L-D < group R-D < group D < group T-D < blank control group < group THP. The nude mice in groups L-D, R-D and D were normal, active and had a healthy appetite. The mice in groups T-D and THP were lethargic, less active and showed loss of appetite, and their caudal vein was easy to stimulate. The mice in the blank control group were sacrificed during the third week or when their tumors developed ulceration. Compared with the blank control group, c-Myc gene expression was reduced in the tumors of the five experimental groups.
The results showed that DC-CIK cells stimulated by different methods were highly effect against MDA-MB-231 breast cancer stem cells in nude mice in all groups, especially in group L-D. DC-CIK immunotherapy may provide a new strategy for the clinical treatment of breast cancer.
比较不同方法负载DC-CIK细胞用于MDA-MB-231乳腺癌干细胞免疫治疗的效果和安全性。
利用乳腺癌干细胞在BALB/c裸鼠中建立乳腺癌模型。将所有小鼠随机分为六组，每组三只裸鼠：空白对照组、DC-CIK组（D组）、MDA-MB-231 CSC全细胞裂解物DC-CIK组（L-D组）、MDA-MB-231 CSC RNA DC-CIK组（R-D组）、THP DC-CIK组（T-D组）和THP组。D组、L-D组、R-D组和T-D组的裸鼠注射CSCs；4天后，通过尾静脉给小鼠接种1×10(6)个DC-CIK细胞。每周重复注射2次，共三周。THP组和T-D组的小鼠在DC-CIK注射前一天通过尾静脉注射5mg/Kg剂量的THP化疗药物，每周重复一次，共三周。空白对照组的裸鼠注射生理盐水。小鼠安乐死后测量肿瘤的重量和大小。用RT-PCR检测与Akt信号通路相关的关键原癌基因c-Myc的表达。
各组肿瘤生长速率如下：L-D组 < R-D组 < D组 < T-D组 < 空白对照组 < THP组。L-D组、R-D组和D组的裸鼠正常、活跃、食欲良好。T-D组和THP组的小鼠嗜睡、活动减少、食欲不振，且尾静脉容易被刺激。空白对照组的小鼠在第三周或肿瘤出现溃疡时被处死。与空白对照组相比，五个实验组肿瘤中的c-Myc基因表达均降低。
结果表明，不同方法刺激的DC-CIK细胞对所有组裸鼠中的MDA-MB-231乳腺癌干细胞均有高效作用，尤其是L-D组。DC-CIK免疫治疗可能为乳腺癌的临床治疗提供一种新策略。
