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, Cleveland, Ohio 44106-5056, 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 μ 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.