Therapeutic effects of all trans-retinoic acid combined with transarterial chemoembolization on Walker-256 hepatoma in rats.
In order to investigate the inhibitory effects of all trans-retinoic acid (ATRA) on differentiation and apoptosis of Walker-256 hepatocellular carcinoma cells and the therapeutic effects of ATRA combined with transarterial chemoembolization (TACE) on rat Walker-256 transplanted hepatocarcinoma, Walker-256 hepatocarcinoma cell lines were treated with ATRA at different concentrations. After culture for 48 h, the inhibitory rate of cell proliferation was determined by MTT assay; the changes of Fas and Bcl-2 mRNA expression were determined by RT-PCR, and the expression levels of Caspase3 and Caspase8 proteins were detected by Western blot. Twenty-seven Wistar rat models of hepatocarcinoma were set up successfully by implanting Walker-256 cell lines. The tumor volume at the 11th day after implantation (V(preoperation)) was measured by magnetic resonance imaging (MRI). The 27 rats were randomly and equally divided into three groups, and the therapy scheme was performed as follows: group A (ATRA 0.1 mg+mitomycin 0.05 mL+lipiodol 0.05 mL+gelfoam powder 0.025 mg); group B (mitomycin 0.05 mg+lipiodol 0.05 ml+gelfoam 0.025 mg; group C (0.9% NaCl 0.2 mL). After another 11 days, MRI was performed once again to measure the tumor volume (V(postoperation)). The expression of factor and Ki VIII -67 in the tumor tissues was detected by immunohistochemistry. The results showed that ATRA could suppress proliferation of Walker-256 cell lines. After treatment of Walker-256 cell lines with ATRA, the expression of Fas mRNA was significantly up-regulated and the Bcl-2 mRNA was significantly down-regulated by ATRA at the concentration of 10 mumol/L as compared with the control group (P<0.05). After treatment with 10 mumol/L ATRA for 48 h, the Caspase3 and Caspase8 were significantly activated as compared with the control group (P<0.05). Significant difference existed in growth rate among the three groups (P<0.01) and between either two groups (P<0.05). The expression rate of factor VIII and Ki-67 was gradually increased from group A, group B to group C. The study suggests that ATRA could inhibit the proliferation of Walker-256 cells and the effectiveness of the combined therapy (ATRA+TACE) for treating transplanted hepatoma of rats is superior to that of TACE alone.
Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. fangjinlinchn@163.com
Jianlin
J
Fang
Chuansheng
C
Zheng
Hongfang
H
Tao
Hui
H
Zhao
Jianzhuang
J
Ren
Gansheng
G
Feng
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002279:Carcinoma 256, Walker / Q000628:therapy*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D003131:Combined Modality Therapy; D008114:Liver Neoplasms, Experimental / Q000628:therapy*; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D017208:Rats, Wistar; D014212:Tretinoin / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D014212:Tretinoin; C505530:CASP8 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D053181:Caspase 8