Improved ADM Penetration Distance and Therapeutic Efficiency in a Rabbit VX2 Liver Cancer Model by Relaxin Infusion Combined with Transcatheter Chemoembolization Through Hepatic Artery

PURPOSE: To evaluate the adriamycin (ADM) pervasion distance within tumor stroma after relaxin (RLX) infusion through tumor feeding artery and further investigate the therapeutic effects of RLX infusion combined with transcatheter chemoembolization (TACE) on the rabbit VX2 liver cancer, since the chemotherapy impaired due to limited drug distribution hindered by stiffened tumor stroma. MATERIALS AND METHODS: In the first part, rabbits received normal saline (NS), RLX or combined with TACE, and the penetration distance of ADM was measured by immunofluorescence and the matrix metalloproteinases (MMPs) were evaluated by gelatin substrate zymography in each group. In the second part, the rabbits received NS, TACE and RLX combined with TACE, respectively. The tumor growth rates, necrosis rates and intrahepatic metastasis were measured, and hematoxylin-eosin (HE), transferase-mediated dUTP-biotin nick end labelling (TUNEL) and Ki67 staining were conducted in each group. RESULTS: In the first part, the expression of MMP-9 was increased in groups treated by RLX compared with NS group, especially three days after RLX infusion (p=0.001). The ADM penetration distance was significantly increased in groups treated by RLX compared with NS group (p<0.05), and it was farthest three days after RLX infusion. In the second part, compared with the NS and TACE groups, the tumor growth rates, the positive staining rates of Ki67 and the tumor growth rates were significantly decreased in RLX+TACE group (p<0.05). However, the positive staining rates of TUNEL and the tumor necrosis rates were significantly increased (p<0.05), and HE staining also revealed higher necrosis rates. The intrahepatic metastasis indicates no difference between the three groups (p=0.273). CONCLUSION: An increased penetration distance was obtained by RLX infusion through tumor feeding artery, and better therapeutic effects were achieved by RLX combined with TACE.