Dedoussis G, Menounos P, Papadopoulos N, Gounaris A, Karameris A
Center for Thalassemia, Laiko General Hospital, Athens, Greece.
Anticancer Res. 1998 Jul-Aug;18(4C):3081-5.
The development of resistance to cisplatin (CDDP) occurs both in vitro and in vivo. We cultured K562 cells with continuous exposure to gradually increasing doses of CDDP and produced CDDP resistant K562 sublines. CDDP-resistant sublines were found to be cross-sensitive to Mit-C and cross-resistant to DXR and cyclophosphamide. These sublines were tested for their susceptibility to NK-mediated lysis using NK cells isolated from 10 healthy donors and 12 patients with breast cancer. K562/B6 and K562/C9 CDDP-resistant sublines were more resistant (22 +/- 5% and 19 +/- 3% lysis, respectively for Ca patients, and 34 +/- 6 and 31 +/- 5% for healthy donors) than the maternal K562 cells (36 +/- 3% for Ca patients and 55 +/- 5% for healthy individuals). The correlation of cisplatin resistance, with a diminished susceptibility by NK lysis, should permit the selection of patients suitable for cisplatin-based chemotherapy.
顺铂(CDDP)耐药性的产生在体外和体内均会出现。我们用逐渐增加剂量的CDDP持续培养K562细胞,从而产生了对CDDP耐药的K562亚系。发现对CDDP耐药的亚系对丝裂霉素C呈交叉敏感,而对阿霉素和环磷酰胺呈交叉耐药。使用从10名健康供体和12名乳腺癌患者中分离出的NK细胞,检测了这些亚系对NK介导的裂解的敏感性。与亲代K562细胞(癌症患者为36±3%,健康个体为55±5%)相比,K562/B6和K562/C9 CDDP耐药亚系更具抗性(癌症患者分别为22±5%和19±3%的裂解率,健康供体分别为34±6%和31±5%)。顺铂耐药性与NK裂解敏感性降低之间的相关性,应有助于选择适合基于顺铂化疗的患者。