Selective preservation of pemetrexed pharmacological activity in HeLa cells lacking the reduced folate carrier: association with the presence of a secondary transport pathway.

@article{Zhao2004SelectivePO,
  title={Selective preservation of pemetrexed pharmacological activity in HeLa cells lacking the reduced folate carrier: association with the presence of a secondary transport pathway.},
  author={Rongbao Zhao and M. Hanscom and Shrikanta Chattopadhyay and I. David Goldman},
  journal={Cancer research},
  year={2004},
  volume={64 9},
  pages={
          3313-9
        }
}
A methotrexate (MTX)-resistant HeLa subline (R5), developed in this laboratory, with impaired transport due to a genomic deletion of the reduced folate carrier (RFC) was only 2-fold resistant to pemetrexed (PMX), but 200- and 400-fold resistant to raltitrexed (ZD1694) and N(alpha)-(-4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-1-ornithine (PT523), respectively, compared with parental HeLa cells when grown with 2 microM folic acid. When folic acid was replaced with the more physiological 25 nM… 
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Antifolate Resistance in a HeLa Cell Line Associated With Impaired Transport Independent of the Reduced Folate Carrier
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It is demonstrated that RFC-independent transport in HeLa cells at low and neutral pH contributes to antifolate activity and can be diminished by antIFolate selective pressure and the loss of these activities results in marked resistance to PMX, an agent for which there is little or no loss of activity when transport mediated by RFC is abolished.
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Solid tumor-targeted antifolates with PCFT-selective cellular uptake should have enhanced activities toward tumors lacking RFC function, reflecting contraction of THF cofactor pools.
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Lack of Impact of the Loss of Constitutive Folate Receptor α Expression, Achieved by RNA Interference, on the Activity of the New Generation Antifolate Pemetrexed in HeLa Cells
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Constutively expressed FR-α in HeLa cells does not contribute to PMX activity in the presence or absence of RFC function, likely the case in many human solid tumor cell lines.
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