Furukawa T, Kubota T, Murata H, Tanino H, Yuasa S, Morita K, Ueno J, Kozakai K, Yano T
Immunochemical Laboratory, Eiken Chemical Co., Ltd. Tokyo, Japan.
J Surg Oncol. 1998 Nov;69(3):173-7. doi: 10.1002/(sici)1096-9098(199811)69:3<173::aid-jso10>3.0.co;2-h.
Although the mechanism of P-glycoprotein (Pgp)-related resistance of doxorubicin is known, it has not been clarified for other anthracycline derivatives. We have examined the chemosensitivity of gastric cancer tissues to three anthracyclines in relation to Pgp expression.
Sixty-six surgical specimens obtained from patients with gastric cancer were subjected to histoculture drug response assay using doxorubicin (DXR), epirubicin (EPI), and 4'-O-tetrahydropyranyldoxorubicin (pirarubicin; THP). The cutoff concentrations used were 15 microg/ml for DXR and EPI and 17 microg/ml for THP.
A 50% or more inhibition index (I.I.) was regarded as sensitive, at which the correlation rates were 95.8% (23/24) and 74.2% (49/66) for DXR-EPI and DXR-THP, respectively. Twenty-six specimens were immunohistochemically stained with monoclonal antibody to Pgp, with a positive rate of 53.8% (14/26). In Pgp-positive specimens, all cases were resistant to DXR and 28.6% (4/14) of cases were sensitive to THP, while the antitumor activity of EPI was essentially identical to that of DXR.
The expression of Pgp might affect resistance to DXR and EPI, although THP may partially impair this resistance, suggesting the clinical usefulness of THP in treatment of DXR-refractory gastric carcinoma.
尽管已知多柔比星的P-糖蛋白（Pgp）相关耐药机制，但其他蒽环类衍生物的该机制尚未阐明。我们研究了胃癌组织对三种蒽环类药物的化疗敏感性与Pgp表达的关系。
对66例胃癌患者的手术标本进行组织培养药物反应分析，使用多柔比星（DXR）、表柔比星（EPI）和4'-O-四氢吡喃基多柔比星（吡柔比星；THP）。所用的临界浓度为DXR和EPI为15μg/ml，THP为17μg/ml。
抑制指数（I.I.）达50%或更高被视为敏感，此时DXR-EPI和DXR-THP的相关率分别为95.8%（23/24）和74.2%（49/66）。26个标本用抗Pgp单克隆抗体进行免疫组织化学染色，阳性率为53.8%（14/26）。在Pgp阳性标本中，所有病例对DXR耐药，28.6%（4/14）的病例对THP敏感，而EPI的抗肿瘤活性与DXR基本相同。
Pgp的表达可能影响对DXR和EPI的耐药性，尽管THP可能部分削弱这种耐药性，提示THP在治疗对DXR耐药的胃癌中具有临床应用价值。
