Changes of metastatic potential of residual hepatocellular carcinoma in nude mice after in vivo chemotherapy and the corresponding mechanisms / 中华肿瘤杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore the changes of metastatic potential of residual hepatocellular carcinoma (HCC) after in vivo chemotherapy and its mechanism.</p><p><b>METHODS</b>Nude mouse models of orthotopic HCC in the nude mouse livers was established using human hepatocellular carcinoma cell line MHCC97L cells. Oxaliplatin (10 mg/kg, once per week) was administered intraperitoneally (i.p.) to mice in the trial group. Mice in the control group received 0.2 ml of 0.9% sodium chloride on the same days. On day 7 after the third injection, all mice were sacrificed and tumor fragments of equal volume (2 mm×2 mm×2 mm) from each mouse of the oxaliplatin-treated and untreated groups were reinoculated into the livers of each new recipient mouse correspondingly. The growth, metastasis and molecular phenotype of the reinoculated tumors in both groups were determined.</p><p><b>RESULTS</b>In the new recipient mice, compared with untreated tumors, oxaliplatin pre-treated tumors grew significantly slower [(2624.59 ± 491.60) mm(3) vs. (3849.72 ± 827.09) mm(3), P < 0.001], but gave more spontaneous metastasis to the lung (10/12 vs. 3/12, P = 0.012). A decreased expression of E-cadherin and increased expression of N-cadherin, vimentin and transcription factor Snail were detected in the oxaliplatin pre-treated tumors by immunohistochemistry, which provided the evidence of epithelial mesenchymal transition (EMT) in these tumors.</p><p><b>CONCLUSION</b>Residual hepatocellular carcinomas after in vivo chemotherapy grow slower but gain enhanced metastatic potential to the lung, associated with epithelial mesenchymal transition.</p>