Advantage of in vivo chemosensitivity assay to detect vincristine-resistance in a human epidermoid carcinoma xenograft.
Advantage of in vivo chemosensitivity assay to detect vincristine-resistance in a human epidermoid carcinoma xenograft.
复制标题
体内化学敏感性测定检测人表皮样癌异种移植物中长春新碱耐药性的优点。
作者：
Y. Abe;H. Yamazaki;Y. Oshika;R. Suto;A. Tsugu;E. Ota;H. Satoh;Y. Ohnishi;T. Yanagawa;Y. Ueyama;N. Tamaoki;M. Nakamura
我们研究了体外和体内化疗敏感性的人表皮样癌异种移植xeKB 3 -1-R，其中显示多药耐药基因（MDR 1）的过度表达。在体外肿瘤细胞粘附培养系统中，XeKB 3 -1-R对长春新碱（VCR，6%）和阿霉素（DOX，9%）敏感。然而，在体内化疗敏感性试验中，该异种移植物显示对VCR（65%）和DOX（42%）的敏感性降低。xeKB 3 -1-R对VCR和DOX的体内耐药性可被环孢素A（VCR 22%，DOX 11%）逆转。异种移植物xeKB 3 -1-R表达的MDR 1水平显著高于xeKB 3 -1。结果证实xeKB 3 -1-R的多药耐药与体内MDR 1表达增强有关。体外和体内化疗敏感性之间观察到的差异表明，体内敏感性试验更准确地反映了由于实体瘤中低水平MDR 1过表达而产生的耐药性。
We examined both in vitro and in vivo chemosensitivity of the human epidermoid carcinoma xenograft xeKB3-1-R which shows overexpression of the multidrug resistance gene (MDR1). XeKB3-1-R was sensitive to vincristine (VCR, 6%) and doxorubicin (DOX, 9%) in the adhesive tumor cell culture system in vitro. However, this xenograft showed decreased sensitivity to VCR (65%) and DOX (42%) in an in vivo chemosensitivity assay. The in vivo resistance of xeKB3-1-R to both VCR and DOX was reversed by coadministration of cyclosporin A (VCR 22%, DOX 11%). The xenograft xeKB3-1-R expressed significantly higher levels of MDR1 than xeKB3-1. The results confirmed that multidrug resistance in xeKB3-1-R was related to enhanced MDR1 expression in vivo. The observed discrepancies between in vitro and in vivo chemosensitivities suggest that the in vivo sensitivity assay more accurately reflects drug resistance as a result of low-level MDR1 overexpression in solid tumors.