Efficiency of combined blocking of aerobic and glycolytic metabolism pathways in treatment of N1-S1 hepatocellular carcinoma in a rat model
Hooman Yarmohammadi1, Luke R Wilkins2, Joseph P Erinjeri1, Ronald D Novak3, Agata A Exner4, Hanping Wu4, Elena N Petre1, Edward Boas1, Etay Ziv1, John R Haaga3
1 Department of Radiology, Division of Interventional Radiology and Image Guided Therapy, Memorial Sloan Kettering Cancer Center, New York 10065, USA
2 Department of Radiology, University of Virginia, Charlottesville, Virginia, USA
3 Department of Radiology, Case Western Reserve University, USA
4 Department of Radiology, Case Western Reserve University, Case Center for Imaging Research, Cleveland, Ohio 44106 5056, USA
Department of Radiology, Division of Interventional Radiology and Image Guided Therapy, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York 10065
Source of Support: None, Conflict of Interest: None
Background/Aim: The aim of this study was to determine whether the addition of bumetanide (BU), a glycolytic metabolism pathway inhibitor, to arterial embolization improves tumor necrosis of N1-S1 hepatocellular carcinoma in a rat model.
Materials and Methods: N1-S1 tumors were surgically implanted in the liver of 14 Sprague-Dawley rats. The rats were divided into three groups: In control group (n = 5), 1 ml of normal saline was injected intra-arterially. The tumor in the transarterial embolization group (TAE, n = 4) was embolized using 10 mg of 50-150 m polyvinyl alcohol (PVA) particles and embolization plus BU group (TAE + BU, n = 5) were embolized with 10 mg of PVA plus 0.04 mg/kg of BU. Tumor volume was measured using two-dimensional ultrasound before intervention and twice a week afterward. Relative tumor volume after the intervention was calculated as the percentage of preinterventional tumor volume. After 4 weeks of observation, the rats were sacrificed for histopathological evaluation.
Results: No statistically significant difference was detected in the preintervention tumor sizes between the three groups (P > 0.05). In the control group, the relative tumor volume increased to 142.5% larger than baseline measurements. In the TAE group, the tumor volume decreased by 18.2 ± 12.2%. The tumor volume in the TAE + BU group decrease by 90.4 ± 10.2%, which was 72.2% more than in TAE only group (P < 0.0001). Histopathological evaluation demonstrated no residual tumor in the TAE + BU group.
Conclusion: Tumor necrosis significantly increased in N1-S1 tumor that received BU at the time of TAE when compared to TAE alone.