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在兔VX2肝细胞癌模型中,经肝动脉给予索拉非尼和碘油可有效抑制肿瘤生长及肝内转移。

Hepatic arterial administration of sorafenib and iodized oil effectively attenuates tumor growth and intrahepatic metastasis in rabbit VX2 hepatocellular carcinoma model.

作者信息

Zhang Lin, Liu Feng-Yong, Fu Jin-Xin, Duan Feng, Fan Qing-Sheng, Wang Mao-Qiang

机构信息

Department of Interventional Radiology, Chinese PLA General Hospital Beijing 100853, China.

出版信息

Int J Clin Exp Pathol. 2014 Oct 15;7(11):7775-81. eCollection 2014.

Abstract

AIM

To investigate the therapeutic effect of the hepatic arterial administration of sorafenib in rabbit VX-2 hepatocellular carcinoma (HCC) model.

METHODS

Rabbit VX-2 HCC models were established via implanting VX-2 tumors into the livers, and randomly divided into four groups, respectively treated with (1) The hepatic arterial administration of iodized oil alone (TACE-i), (2) The hepatic arterial administration of iodized oil and pharmorubicin (TACE-ip), (3) The hepatic arterial administration of iodized and cis-DDP (TACE-ic), (4) The hepatic arterial administration of iodized and sorafenib (TACE-is). The growth rate and intrahepatic metastasis of implanted VX-2 tumor in each rabbit were measured. Microvessel density (MVD) in the adjacent tissues of implanted VX-2 tumor were estimated by detecting the expression of CD34 and VEGF level in tumor adjacent tissues were also examined by Immunohistochemistry.

RESULTS

Compared with other groups, TACE-is treatment group presented a better effect on inhibiting tumor growth rate and intrahepatic metastasis in rabbit VX-2 HCC model. The angiogenesis (assessed by MVD) in the adjacent tissues were suppressed more dramatically in TACE-is treated group. Moreover, TACE-is treatment did not significantly increase the levels of alanine transaminase and creatinine compared to the group with TACE-i treatment.

CONCLUSION

The hepatic arterial administration of sorafenib and iodized oil (TACE-is) effectively attenuates tumor growth and intrahepatic metastasis in rabbit VX-2 HCC model without obvious hepatic and renal toxicity. One of the related mechanisms may be due to the inhibition of angiogenesis in the adjacent tissues. Our data indicated that TACE-is may be a secure and effective treatment for HCC.

摘要

目的

探讨索拉非尼肝动脉给药对兔VX-2肝癌(HCC)模型的治疗效果。

方法

通过将VX-2肿瘤植入兔肝脏建立兔VX-2 HCC模型,并随机分为四组,分别接受以下治疗:(1)单纯肝动脉注射碘化油(TACE-i);(2)肝动脉注射碘化油和表柔比星(TACE-ip);(3)肝动脉注射碘化油和顺铂(TACE-ic);(4)肝动脉注射碘化油和索拉非尼(TACE-is)。测量每只兔体内植入的VX-2肿瘤的生长速度和肝内转移情况。通过检测肿瘤邻近组织中CD34的表达来估计植入的VX-2肿瘤邻近组织中的微血管密度(MVD),并通过免疫组织化学检测肿瘤邻近组织中的VEGF水平。

结果

与其他组相比,TACE-is治疗组在抑制兔VX-2 HCC模型的肿瘤生长速度和肝内转移方面表现出更好的效果。TACE-is治疗组中,邻近组织中的血管生成(通过MVD评估)受到更显著的抑制。此外,与TACE-i治疗组相比,TACE-is治疗并未显著增加丙氨酸转氨酶和肌酐水平。

结论

索拉非尼与碘化油肝动脉给药(TACE-is)可有效减轻兔VX-2 HCC模型中的肿瘤生长和肝内转移,且无明显肝肾毒性。相关机制之一可能是由于抑制了邻近组织中的血管生成。我们的数据表明,TACE-is可能是一种安全有效的HCC治疗方法。

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