Scientific Abstracts: Basic Science and Technology
Objective: To determine whether matrix metalloproteinase (MMP) inhibitor batimastat (BB-94) could inhibit the progression of liver tumor after radiofrequency ablation (RFA) and achieve better therapeutic efficacy in an animal model.
Methods: In vitro experiments, the proliferation of H22 cells was detected by CCK8 method and cell migration was detected by Transwell method. Next, H22 murine liver tumors were used for in vivo experiments. First, 32 mice with one tumor were randomized into four groups (n=8 each group): control (PBS only), RFA alone (65℃, 5min), BB-94 (30 mg/kg), RFA+BB-94. The growth rate of the residual tumor and the end point survival were estimated and the pathologic changes were compared. Secondly, a total of 48 tumors in 24 animals were randomized into three groups (n= 8 each group): control (PBS only), RFA alone, RFA+BB-94. Each mouse was implanted two tumors subcutaneously, one tumor was ablated and the other was evaluated for distant metastasis after applying BB-94.
Results: In vitro, the proliferation assay demonstrated that the H22 cells had significantly higher proliferation rate in the heat group than the control group (1.27±0.08 vs 0.82±0.07, P=0.008), and it could be inhibited by BB-94 (0.67±0.06 vs 0.37±0.01, P=0.015). In the cell migration assay, the H22 cells demonstrated enhanced invasive ability after heat experiment (33.7±2.1 vs 19.7±4.9, P=0.011). And it could be significantly suppressed after treated with BB-94 (32.3±3.5 vs 23.0±4.6, P=0.009). With one tumor animal, the growth rate of the residual tumor in the BB-94+RFA group was slower than that in the RFA alone group (P=0.003). And combination of BB-94 could significantly prolong the survival of the mice (40.3±1.4d vs 47.1±1.3d, P =0.002). The expression of MM9, Collagen I and VEGF at the coagulation margin were decreased after combined with BB-94. With two tumors animal, the tumor growth rate of metastasis tumor in the BB-94+RFA group was lower than that in the RFA group (P<0.001).
Conclusions: BB-94 combined with RFA reduced the invasiveness of the tumor and improved the endpoint survival. It also helped to suppress the growth rate of metastasis tumor after RFA. Our data suggested that targeting the MMP process with the specific inhibition could increase overall ablation efficacy.