Ishimura H
First Department of Surgery, Hokkaido University, School of Medicine, Sapporo, Japan.
Hokkaido Igaku Zasshi. 1996 Nov;71(6):689-98.
10 HCC cell lines and 122 surgically resected HCC were studied on chemosensitivity to 6 anticancer agents. Succinic dehydrogenase inhibition test was used for evaluating chemosensitivity of HCC. The HCC cell lines were positive in sensitivity to the most anticancer agents except 5-FU. Sensitivity of resected HCC specimens was positive in 17/42 (40.5%) to exposed to VP-16, in 21/57 (36.8%) to IFM, but also it was positive in 40/46 (87.0%) of the non-cancer tissue of the same liver exposed to VP-16 and in 33/60 (55.0%) to IFM. So VP-16 and IFM were probably considered to injure the residual liver after hepatectomy. In immunostainings of P-gp, GST-pi, MT, and P-450 of HCC cell lines, the expression of P-gp correlated with MDR1 mRNA and chemosensitivity test to ADM. Correlation between the expression of GST-pi and chemosensitivity test to ADM and CDDP were considered to be probably recognized. However, in surgically resected HCC, correlation among those factors was not observed.
P-gp, MDR1 gene and GST-pi have probably a role in drug resistance in HCC. Selection of anticancer agents after chemosensitivity tests on both HCC and normal tissue of liver should be performed. We need more investigation for how the results of chemosensitivity test correlate with clinical effectiveness.
对10种肝癌细胞系和122例手术切除的肝癌组织进行了6种抗癌药物的化疗敏感性研究。采用琥珀酸脱氢酶抑制试验评估肝癌的化疗敏感性。除5-氟尿嘧啶外,肝癌细胞系对大多数抗癌药物敏感。切除的肝癌标本对VP-16的敏感性为17/42(40.5%),对异环磷酰胺的敏感性为21/57(36.8%),但同一肝脏的非癌组织对VP-16的敏感性为40/46(87.0%),对异环磷酰胺的敏感性为33/60(55.0%)。因此,VP-16和异环磷酰胺可能会损伤肝切除术后的残余肝脏。在肝癌细胞系的P-糖蛋白、谷胱甘肽S-转移酶π、金属硫蛋白和P-450免疫染色中,P-糖蛋白的表达与MDR1 mRNA及对阿霉素的化疗敏感性试验相关。谷胱甘肽S-转移酶π的表达与对阿霉素和顺铂的化疗敏感性试验之间的相关性可能得到认可。然而,在手术切除的肝癌中,未观察到这些因素之间的相关性。
P-糖蛋白、MDR1基因和谷胱甘肽S-转移酶π可能在肝癌耐药中起作用。应对肝癌及肝正常组织进行化疗敏感性试验后再选择抗癌药物。我们需要更多研究来探讨化疗敏感性试验结果与临床疗效之间的关系。