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Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
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[Establishment of Drug-resistant Acute Lymphoblastic Leukemic Cell Lines and Their Resistance Mechanism]

Tian-Tian Li1, Li Zhang1, Shan-Dong Tao1

  • 1Department of Hematology, Huai'an First People's Hospital Affiliated to Nanjing Medical University, Huai'an 223300, Jiangsu Province, China; Key Laboratory of Hematology, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.

Zhongguo Shi Yan Xue Ye Xue Za Zhi
|June 29, 2018
PubMed
Abstract

Insights

Two adriamycin (ADR)-resistant acute lymphoblastic leukemia (ALL) cell lines were established and demonstrated cross-resistance to other chemotherapies. Overexpression of P-glycoprotein (P-gp) and MDR1 may contribute to this drug resistance.

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Acute lymphoblastic leukemia (ALL) remains a significant challenge in pediatric and adult oncology.
  • Drug resistance is a major obstacle to successful ALL treatment, necessitating the development of models to study resistance mechanisms.
  • Adriamycin (ADR) is a key chemotherapeutic agent used in ALL treatment, but its efficacy can be limited by acquired resistance.

Purpose of the Study:

  • To establish novel adriamycin (ADR)-resistant acute lymphoblastic leukemia (ALL) cell lines.
  • To investigate the underlying mechanisms of ADR resistance in these newly developed ALL cell lines.

Main Methods:

  • Adriamycin (ADR)-resistant ALL cell lines (SUP-B15/ADR and RS4;11/ADR) were generated by exposing parental cells to increasing ADR concentrations.
  • Cell viability was assessed using the CCK-8 assay.
  • Expression levels of P-glycoprotein (P-gp) and multidrug resistance gene 1 (MDR1) were determined via Western blot and RT-qPCR, respectively.

Main Results:

  • Successfully established SUP-B15/ADR and RS4;11/ADR cell lines with resistance indexes of 14.088±0.763 and 10.473±1.024, respectively.
  • These resistant cell lines exhibited cross-resistance to cytarabine and etoposide.
  • Significantly higher expression of P-gp and MDR1 was observed in the drug-resistant cell lines compared to their wild-type counterparts.

Conclusions:

  • The successful establishment of ADR-resistant ALL cell lines provides valuable tools for studying leukemia drug resistance.
  • The observed overexpression of MDR1 and P-gp suggests their critical role in mediating adriamycin resistance in ALL.
  • These findings contribute to a better understanding of the molecular mechanisms of chemotherapy resistance in acute lymphoblastic leukemia.

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