Abstract:
Glioma is one of the most frequently seen malignant tumors in the central nervous system. Alkylating agents such as 1,3-bis( 2-chloroethyl )- 1-nitrosourea ( BCNU ) are among the most effective cytotoxic agents for these patients, but the responses remain very poor. The adenosine triphosphate binding cassette ( ABC ) transporter family, whose products represent membrane proteins, have the capability to use energy to drive the transporters of various molecules across the cellular membrane, and are confirmed to be associated with anticancer drug transporters. At present, 11 ABC transporters have been found to be involved in drug resistance. In the present study, the glioma cell lines SWOZ1 and SWOZ2, which were isolated and cloned from the same parental cell line SWO38, were used to investigate the relationship between the expression of 11 ABC transporters and BCNU resistance in gliomas. Methods: The glioma cell line SWOZ2, which is sensitive to BCNU treatment, was taken as the control, and glioma cell line SWOZ1, which is resistant to BCNU, was taken as the intrinsic resistant cell line. BCNU-resistant cells SWOZ2/B, derived from SWOZ2, were taken as the acquired resistant cell line. A CCK-8 assay was used to determine the growth curve of the cells, and also the IC50 values and resistance indices ( RI ) to BCNU of each cell line. Quantitative RT-PCR was used to evaluate the modulation of the expression of the eleven ABC transporters related to drug resistance in these cell lines. Results: No significance was found between the growth curves of the cell lines. Based on the results of the CCK-8 assay, the IC50 value of the cell lines SWOZ1 and SWOZ2/B against BCNU was ( 16.17 ± 1.62 ) and ( 22.38 ± 1.08 ) μg/mL, respectively. The resistance of SWOZ1 and SWOZ2/B were 4.7-fold and 6.5-fold more than that of the cell line SWOZ2 ( 3.47 ± 0.86 ) μg/mL, respectively. The results of quantitative RT-PCR revealed that only ABCG1 was overexpressed both in the intrinsic and acquired BCNU-resistant cell lines SWOZ1 and SWOZ2/B, compared with the BCNU-sensitive cell line SWOZ2. The upregulation of ABCG1 expression was 4.1-fold and 4.4-fold in the SWOZ1 and SWOZ2/B cell lines than in the cell line SWOZ2. Conclusion: Our data indicate that ABCG1 may play an important role in the resistance of glioma cells to BCNU.