Transarterial chemoembolization of hepatocellular carcinoma in a rat model: the effect of additional injection of survivin siRNA to the treatment protocol

Abstract

BackgroundTransarterial chemoembolization is one of the most widely accepted interventional treatment options for treatment of hepatocellular carcinoma. Still there is a lack of a standard protocol regarding the injected chemotherapeutics. Survivin is an inhibitor of Apoptosis protein that functions to inhibit apoptosis, promote proliferation, and enhance invasion. Survivin is selectively up-regulated in many human tumors. Small interfering RNA (siRNA) can trigger an RNA interference response in mammalian cells and induce strong inhibition of specific gene expression including Survivin. The aim of the study is to assess the effectiveness of the additional injection of Survivin siRNA to the routine protocol of Transarterial Chemoembolization (TACE) for the treatment of hepatocellular carcinoma in a rat model.MethodsThe study was performed on 20 male ACI rats. On day 0 a solid Morris Hepatoma 3924A was subcapsullary implanted in the liver. On day 12 MRI measurement of the initial tumor volume (V1) was performed. TACE was performed on day 13. The rats were divided into 2 groups; Group (A, n = 10) in which 0.1 mg mitomycin, 0.1 ml lipiodol and 5.0 mg degradable starch microspheres were injected in addition 2.5 nmol survivin siRNA were injected. The same agents were injected in Group (B,=10) without Survivin siRNA. MRI was repeated on day 25 to assess the tumor volume (V2). The tumor growth ratio (V2/V1) was calculated. Western blot and immunohistochemical analysis were performed.ResultsFor group A the mean tumor growth ratio (V2/V1) was 1.1313 +/− 0.1381, and was 3.1911 +/− 0.1393 in group B. A statistically significant difference between both groups was observed regarding the inhibition of tumor growth (P < 0.0001) where Group A showed more inhibition compared to Group B. Similarly immunohistochemical analysis showed significantly lower (p < 0.002) VEGF staining in group A compared to group B. Western Blot analysis showed a similar difference in VEGF expression (P < 0.0001).ConclusionThe additional injection of Survivin siRNA to the routine TACE protocol increased the inhibition of the hepatocellular carcinoma growth in a rat animal model compared to regular TACE protocol.

TGF-β1 signaling pathway serves a role in HepG2 cell regulation by affecting the protein expression of PCNA, gankyrin, p115, XIAP and survivin

“…XIAP, an important member of the IAP family, possesses inhibitory activity and serves an important role in cell apoptosis (19,20). Survivin, a novel member of the IAP family with the lowest relative molecular weight, is the most potent suppressor of apoptosis that has been identified so far (21). However, there are currently few studies concerning the association between TGF-β1 and PCNA, gankyrin, p115, XIAP and survivin in liver cancer.…”

“…Conversely, TGF-β1 expression levels in patients with leukemia are significantly decreased compared with healthy subjects (17). Cell growth, the cell cycle and apoptosis are closely associated with the genesis and development of liver cancer, and multiple factors are involved in their regulation, including proliferating cell nuclear antigen (PCNA), gankyrin, general vesicular transport factor p115 (p115), X-linked inhibitor of apoptosis protein (XIAP), survivin and caspase-3 (18)(19)(20)(21). PCNA is a highly conserved protein; in addition to DNA replication, the functions of PCNA are associated with other vital cellular processes, including chromatin remodeling, DNA repair, sister-chromatid cohesion and cell cycle control (22).…”

Antigens from H22 cell mutation induced by lentinan are correlated with HCC immunoprophylaxis

“…We need to co-culture cancer cells with lentinan. H22 cells suspension (1×10 7 ) and lentinan solution (170μL/mg). The co-cultures were cultured at 37 ℃ and 5% CO 2 for 48 hours.…”

“…The emergence of effector T cells after surgical transplantation reduces the risk of recurrence, which is the key to antibody therapy. The combination of monoclonal antibody (mAbs) or chemotherapy and transarterial chemoembolization are the main methods to improve the overall survival rate of HCC patients [7]. Tumor associated antigen (TAA) is a non-speci c antigen, and its expression imbalance leads to immune response de ciency.…”

Association of hepatic vein Lipiodol tram-track sign during transcatheter arterial chemoembolization with perioperative death

“…Because of its rapid invasive growth and complication of liver cirrhosis, HCC usually has a poor prognosis. 1 , 2 Available options for unresectable tumours include interventional therapies that aim to downstage and downsize the tumours, 3 slow tumour development, prolong patient survival, and improve quality of life. Options for transarterial treatment include transcatheter arterial chemoembolization (TACE), bland embolization, radioembolization, and transarterial ethanol ablation.…”