Insufficient radiofrequency ablation therapy may induce further malignant transformation of hepatocellular carcinoma
Insufficient radiofrequency ablation therapy may induce further malignant transformation of hepatocellular carcinoma
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DOI：
10.1007/s12072-007-9040-3
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发表时间：
2008-03-01
影响因子：
6.6
通讯作者：
Itoh, Fumio
中科院分区：
文献类型：
--
作者：
Obara, Koichi;Matsumoto, Nobuyuki;Itoh, Fumio
背景肝细胞癌射频消融(RFA)是一种通过产生凝固性坏死区来杀死肿瘤组织的热消融技术。近来有报道认为射频消融可能导致局部复发，并伴有侵袭性表型和不良预后，提示射频消融可能导致进一步的肝细胞癌恶变。然而，RFA对肝癌细胞的生物学效应还没有被直接分析。本研究的目的是确定RFA相关类型的热应激是否会诱导肝癌细胞恶性转化。方法我们测定了3种肝癌细胞系(HepG2、Alexander和Huh7)对10min热处理的敏感性。然后，我们确定了产生耐热支线的温度。我们建立并扩大了在热处理中幸存下来的子系。结果经48℃处理后，细胞全部死亡，而经49℃处理后，Alexander和Huh7全部死亡。我们为每个亲本细胞系产生了20个亚系。HepG2亚系HepG2#18的增殖速度比亲代HepG2快100%。此外，HepG2#18在50℃处理后存活，而亲本HepG2在48℃或更高温度处理后全部死亡。结论即使是一次热处理也可以诱导肝癌细胞系进一步转化。我们的结果表明，RFA对肝癌的治疗不足，使某些细胞得以存活，可能会在体内诱导进一步的恶性转化。
Background Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is a thermoablative technique to kill tumor tissue by generating areas of coagulative necrosis. Recent reports have raised concern that RFA may lead to a local recurrence of HCC with an aggressive phenotype and unfavorable prognosis, suggesting that RFA may induce further malignant transformation of HCC. However, the biological effects of RFA on HCC cells have not been directly analyzed. The aim of this study was to determine whether heat stress of the type associated with RFA induces malignant transformation of HCC.Methods We assessed the sensitivity of three HCC cell lines (HepG2, Alexander, and Huh7) to heat treatment for 10 min. We then determined the temperature at which a heat-resistant subline can be generated. We established and expanded sublines that survived heat treatment. And their proliferation rates, heat sensitivities, and invasive capacities were further examined.Results All HepG2 died after 48 degrees C treatment, whereas 49 degrees C treatment was required to kill all Alexander and HuH7. We generated 20 sublines for each parental cell line. A HepG2 subline, HepG2#18, proliferated 100% faster than parental HepG2. Moreover, HepG2#18 survived after 50 degrees C treatment, whereas all parental HepG2 died after heat treatments at 48 degrees C or higher.Conclusion Our results showed that even a single heat treatment could induce further transformation of an HCC cell line. Our results suggest that an insufficient treatment of HCC by RFA that enables survival of some cells might induce further malignant transformation in vivo.