Influence of monoacylglycerol lipase on growth of nude mice xenograft tumor of human hepatocellular carcinoma and related mechanism

Objective To investigate the role and mechanism of action of monoacylglycerol lipase ( MAGL) on the growth of nude mice xenograft tumor of human hepatocellular carcinoma ( HCC) . Methods The transplanted SMMC-7721 cells were divided into SMMC-7721 WT group ( without treatment) , SMMC-7721 MAGL-KDgroup ( with MAGL silencing) , SMMC-7721 MAGL-OEgroup ( with MAGL overexpression) , and SMMC-7721 Vectorgroup ( transfected with empty vector) . A total of 27 male BALB/c nude mice were randomly divided into group A ( 12 mice injected with the cells in the SMMC-7721 WTgroup) , group B ( 5 mice injected with the cells in the SMMC-7721 MAGL-KD group) , group C ( 5 mice injected with the cells in the SMMC-7721 MAGL-OEgroup) , and group D ( 5 mice injected with the cells in the SMMC-7721 Vectorgroup) . The mice in group A were further divided into groups A1 ( control group) , A2 ( treated with high-fat diet and JZL184, a specific inhibitor of MAGL) , and A3 ( fed with high-fat diet) , with 4 mice in each group. The four groups were compared in terms of the change in tumor volume and the expression of proliferating cell nuclear antigen ( PCNA) , metal matrix proteinase-2 ( MMP-2) , lysophosphatidic acid ( LPA) , and prostaglandin E2 ( PGE2) in tumor. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the SNK-q test was used for further comparison between two groups. Results There was a significant difference in the relative protein expression of MAGL between the SMMC-7721 WTgroup, the SMMC-7721 MAGL-KDgroup, and the SMMC-7721 MAGL-OEgroup ( 0. 377 ± 0. 026 vs 0. 182 ± 0. 055 vs 0. 689 ± 0. 019, F = 33. 382, P < 0. 001) ; compared with the SMMC-7721 WTgroup, the SMMC-7721 MAGL-KDgroup had significantly lower protein expression of MAGL and the SMMC-7721 MAGL-OEgroup had significantly higher expression ( P < 0. 05) . There was a significant difference in the size of subcutaneous xenograft tumor between groups A, B, C, and D ( 4236. 125 ± 1284. 283 mm3 vs 1883. 375 ± 552. 977 mm3 vs 10 146. 061 ± 1842. 264 mm3 vs 4307. 452 ± 2070. 708 mm3, F= 6. 804, P = 0. 023) . Group C had a lower growth rate of subcutaneous xenograft tumor than group A ( P < 0. 05) , and group B had a higher growth rate than group A ( P < 0. 05) . There were significant differences between groups A, B, and C in the levels of PCNA ( 25 843.821 ± 4201. 310 vs 17 426. 95 ± 5139. 202 vs 39 753. 103 ± 5721. 444, F = 21. 482, P < 0. 001) and MMP-2 ( 52 841. 621 ± 4339. 253 vs35 511. 451 ± 8251. 423 vs 68 274. 731 ± 6418. 594, F = 11. 526, P < 0. 001) ; group B had significantly lower levels of PCNA and MMP-2 than group A ( P < 0. 05) , and group C had significantly higher levels than group A ( P < 0. 05) . There was a significant difference in tumor volume between groups A1, A2, and A3 ( 23 476. 289 ± 483. 872 mm3 vs 18 593. 851 ± 1385. 805 mm3 vs 37 703. 198 ± 2925. 254 mm3, F = 47. 371, P = 0. 004) . Compared with group A1, group A3 had a significantly higher growth rate of subcutaneous xenograft tumor ( P < 0. 05) and group A2 had a significantly lower growth rate ( P < 0. 05) . There was a significant difference in the level of PGE2 between groups A1, A2, and A3 ( 0. 109 ± 0. 023 μmol/L vs 0. 056 ± 0. 010 μmol/L vs 0. 168 ± 0. 024 μmol/L, F = 16. 492, P < 0. 001) ; group A3 had a significantly higher level of PGE2 than group A1 ( P < 0. 05) , and group A2 had a significantly lower level than group A1 ( P < 0.05) . There was a significant difference in the level of PGE2 between groups B, C, and D ( 0. 069 ± 0. 025 μmol/L vs 0. 175 ± 0. 023 μmol/L vs 0. 096 ± 0. 019 μmol/L, F = 31. 550, P < 0. 001) ; group B had a significantly lower level of PGE2 than group D ( P < 0. 05) , and group C had a significantly higher level than group D ( P < 0. 05) . Conclusion MAGL can promote the growth of subcutaneous xenograft tumor of HCC by regulating PGE2, suggesting that MAGL might become a potential target for HCC treatment in future.