Collateral resistance or sensitivity of human larynx carcinoma HEp2 cells resistant to cis-dichlorodiammineplatinum (II) or vincristine sulfate.

Human larynx carcinoma HEp2 cells in tissue culture were repeatedly treated with two chemotherapeutic agents which exhibit distinct mechanisms of action and which differ in mechanisms underlying resistance: cis-dichlorodiammineplatinum (II) (cis-DDP) and vincristine sulfate (VCR). Two schedules of resistance development were used: Acute (cells repeatedly treated with drug for 1 hour in serum-free medium: CA15 and VA15 cells), and continuous (repeatedly treated for 24 hours in complete medium: CK15 and VK15 cells). The sensitivity of cis-DDP resistant (CA15 and CK15 cells) and VCR resistant (VA15 and VK15 cells) sublines to cis-DDP VCR, methotrexate (MTX) and gamma rays was determined by survival assay. The results showed that all sublines became resistant to MTX. Cis-DDP resistant cells became cross-resistant to VCR too. Of VCR resistant sublines, only VK15 cells changed (increased) their sensitivity to cis-DDP. Resistant sublines (except CA15) became sensitive to gamma rays. The degree of resistance or collateral resistance/sensitivity depended on the chemotherapeutic agent used for selection and on the schedule of resistance development. The present data support the idea of complexity of resistance phenomenon. They also emphasize the difficulty and importance of judicious choice of agents that should be given in combined therapy of tumors.