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Updated: Jun 22, 2025

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Down-regulation of ABCB1 in Everolimus-resistant Renal Cell Carcinoma Cells

Yuko Nakayama1, Aya Ino2, Kazuhiro Yamamoto3

  • 1Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Japan.

Anticancer Research
|June 26, 2024
PubMed
Abstract

Insights

Everolimus-resistant renal cell carcinoma cells show cross-resistance to many chemotherapy drugs. However, these cells become more sensitive to paclitaxel and doxorubicin, with decreased ABCB1 mRNA expression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Established everolimus-resistant renal cell carcinoma cell lines (Caki/EV and 786/EV) from parental Caki-2 and 786-O cells.
  • These resistant cells exhibit cross-resistance to mTOR inhibitors and erlotinib.
  • Sensitivity to classical and cytotoxic anticancer drugs in these resistant cells was previously uncharacterized.

Purpose of the Study:

  • To investigate the sensitivity of everolimus-resistant Caki/EV and 786/EV cells to a panel of classical and cytotoxic anticancer drugs.
  • To compare the drug sensitivity profiles of resistant cells against their respective parental cell lines.

Main Methods:

  • Utilized the WST-1 colorimetric assay to evaluate drug sensitivity.
  • Employed SYBR® green-based quantitative reverse transcription-polymerase chain reaction (RT-PCR) to measure mRNA expression levels.
  • Compared drug sensitivity and mRNA expression between resistant and parental cell lines.

Main Results:

  • Sensitivity varied across tested drugs; carboplatin and SN-38 sensitivity remained comparable.
  • Decreased sensitivity was observed for vinca alkaloids, etoposide, 5-fluorouracil, and cisplatin in resistant cells.
  • Remarkable enhanced sensitivity to paclitaxel and doxorubicin was noted in resistant cells, potentially linked to ABCB1 mRNA down-regulation.

Conclusions:

  • Everolimus-resistant renal cell carcinoma cells display cross-resistance to various chemotherapy agents.
  • A significant increase in sensitivity to paclitaxel and doxorubicin was observed in resistant cells.
  • Long-term everolimus exposure led to down-regulation of ABCB1 mRNA in these resistant cell lines.
Keywords:
ABCB1down-regulationeverolimusmTORrenal cell carcinoma

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