Role of RLIP76 in lung cancer doxorubicin resistance: II. Doxorubicin transport in lung cancer by RLIP76

  • Authors:
    • Sanjay Awasthi
    • Sharad S. Singhal
    • Jyotsana Singhal
    • Jizhong Cheng
    • Piotr Zimniak
    • Yogesh C. Awasthi
  • View Affiliations

  • Published online on: April 1, 2003     https://doi.org/10.3892/ijo.22.4.713
  • Pages: 713-720
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

ATP-dependent transport of doxorubicin (DOX) by recombinant human RLIP76 has been demonstrated previously in reconstituted proteoliposomes. In the preceding communication, we demonstrated that the ATPase activity of RLIP76 was 2-fold higher in NSCLC as compared with SCLC, and it correlated with their inherent DOX resistance. Present studies were performed to determine whether greater ATPase activity of RLIP76 in NSCLC translated into greater RLIP76 mediated DOX transport, and to determine the overall contribution of RLIP76 toward total DOX transport. Consistent with the greater RLIP76 ATPase activity in NSCLC, DOX transport in artificial proteoliposomes reconstituted with purified RLIP76 from NSCLC was 1.8-fold greater than in SCLC. Anti-RLIP76 antibodies completely abrogated DOX transport in these RLIP76 proteoliposomes, whereas anti-MRP or anti-Pgp antibodies had no effect on transport. DOX transport studies in crude membrane vesicles from SCLC and NSCLC also showed a 2.1-fold higher rate of transport in NSCLC as compared with SCLC. Anti-RLIP76 IgG, which recognized only RLIP76 in crude extracts of both SCLC and NSCLC, inhibited 67±4% (n=12 cell lines) of total DOX transport in crude membrane vesicles from both SCLC and NSCLC. Inhibition of DOX transport by anti-MRP and anti-Pgp antibody was 35±7% (n=12) and 2±0.3% (n=12), respectively. The mixture of the three antibodies inhibited DOX transport by 95±3% (n=12). These studies demonstrate that DOX transport activity of RLIP76 is significantly greater in NSCLC as compared with SCLC, and that RLIP76 is the major DOX transporter in lung cancer cell lines.

Related Articles

Journal Cover

April 2003
Volume 22 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Awasthi S, Singhal SS, Singhal J, Cheng J, Zimniak P and Awasthi YC: Role of RLIP76 in lung cancer doxorubicin resistance: II. Doxorubicin transport in lung cancer by RLIP76. Int J Oncol 22: 713-720, 2003.
APA
Awasthi, S., Singhal, S.S., Singhal, J., Cheng, J., Zimniak, P., & Awasthi, Y.C. (2003). Role of RLIP76 in lung cancer doxorubicin resistance: II. Doxorubicin transport in lung cancer by RLIP76. International Journal of Oncology, 22, 713-720. https://doi.org/10.3892/ijo.22.4.713
MLA
Awasthi, S., Singhal, S. S., Singhal, J., Cheng, J., Zimniak, P., Awasthi, Y. C."Role of RLIP76 in lung cancer doxorubicin resistance: II. Doxorubicin transport in lung cancer by RLIP76". International Journal of Oncology 22.4 (2003): 713-720.
Chicago
Awasthi, S., Singhal, S. S., Singhal, J., Cheng, J., Zimniak, P., Awasthi, Y. C."Role of RLIP76 in lung cancer doxorubicin resistance: II. Doxorubicin transport in lung cancer by RLIP76". International Journal of Oncology 22, no. 4 (2003): 713-720. https://doi.org/10.3892/ijo.22.4.713