Abstract

The MDR1 gene is frequently over-expressed in cell lines selected for multidrug resistance and certain human tumors. We correlated MDR1 gene expression with DST patterns of 6 cancer cell lines from previously untreated patients. MDR1 RNA was measured by a slot blot analysis. The concentrations of 5 drugs (etoposide, colchicine, doxorubicin, vincristine and 5-fluorouracil) that inhibited 50g of cell growth (IC50 values) were determined by the semi-automated MTT assay. Contral cell lines included KB-3-1 (sensitive) and KB-8-5 (resistant). DST indices' were calculated as follows: IC., of test cell/IC,. of KB-3-1. There was no correlation between MDR1 RNA levels and 5-fluorouracil sensitivity. Results of the other drugs (which are substrates for the MDR1 gene product); MDRI RNA DST Index Cell line Type (unit) (median) (range) KB-3-1 Control 1 1 (None) KB-8-5 Control 30 10 (7-209) SNU-1 Gastric Ca ~1 1.3 (1.0-1.4) SNUH-17 Cervix Ca ~1 3.5 (2.2-4.4) SNUH-46 Laryngeal Ca ~1 5.5 (1.8-17) SNU-47 Bone sarcoma ~1 24 (1.7-545) SNU-C4 Colorectal Ca. 30 48 (4.3-150) SNU-61 Colorectal Ca. 10 105 (2.1-440) We conclude: 1) There is no apparent relationship between MDR1 RNA levels and in vitro sensitivity to 5-fluorouracL 2) With 5 carcinoma cell lines (but not with the sarcoma line) there is an apparent relationship between MDR1 RNA levels and in vitro sensitivities to the other 4 drugs tested.