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Dihydrofolate Reductase Transcript Level Is Not Suitable for Methotrexate-Resistance Prediction in Choriocarcinoma Cell Line
  1. Bing Han, MD*,
  2. Yang Xiang, MD*,
  3. Yun Wang, BD,
  4. Zheng Wang, PhD,
  5. Hao Zhang, BD* and
  6. Shangzhi Huang, MD
  1. *Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; and
  2. Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, People's Republic of China.
  1. Address correspondence and reprint requests to Yang Xiang, MD, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, People's Republic of China. E-mail: xiangyang65{at}gmail.com.

Abstract

Introduction: To assess whether dihydrofolate reductase (DHFR) expression is correlated with the concentration of methotrexate (MTX) exposure and the resistance index during the establishment of MTX-resistant human choriocarcinoma JeG-3 cell line.

Methods: Two series of different MTX-resistant JeG-3 sublines were established by intermittent- and consecutive-inducing methods. Quantitative real-time reverse transcription polymerase chain reaction was used to measure DHFR messenger RNA expression in the sublines during different concentrations of MTX exposure. β-Human chorionic gonadotropin (β-HCG) secretion in these cell lines were detected by using chemoluminescence method.

Results: In the 2 series of MTX-resistant cell lines, the same dynamic profiling of β-HCG secretion and DHFR transcript level were found: At a certain range of concentration, the upward β-HCG secretion and the messenger RNA level of DHFR were correlated with the dose of MTX exposing. However, once the concentration of MTX exceeded this range, the expression would not increase but decrease sharply. According to the concentration of MTX exposure from low to high, the multiples of β-HCG increases were 1.86-, 5.15-, 8.38-, 64.17-, 2.6-, and 0.78-fold for intermittent induction and 22.05-, 6.12-, 5.80-, and 1.77-fold for continuous induction; the multiples of DHFR gene expression increases were 12.84-, 99.02-, 129.01-, 177.63-, 420.78-, and 86.09-fold for intermittent induction and 9.59-, 20.56-, 96.05-, and 58.72-fold for continuous induction.

Conclusions: The transcript level of DHFR gene only correlated with MTX drug resistance at a certain phase. It would be of limited use as a biomarker for the MTX-based chemoresistance prediction.

  • Choriocarcinoma
  • MTX
  • JeG-3 cell line
  • Chemoresistance
  • Dihydrofolate reductase

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Footnotes

  • This work was supported by The Nature Science Foundation of China, project number 30973178.

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