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Rucaparib antagonize multidrug resistance in cervical cancer cells through blocking the function of ABC transporters

Zhen Chen1, Kaijian Ling2, Yingjun Zhu3

  • 1Southwest Hospital, The First Affiliated Hospital of Third Military Medical University, Chongqing, China; The Tianjin Center Hospital of Obstetrics & Gynaecology, Tianjin, China.

Gene
|July 28, 2020
PubMed

Insights

Rucaparib, a PARP inhibitor, overcomes multidrug resistance (MDR) in cervical cancer by blocking ATP-binding cassette (ABC) transporters. This combination therapy shows potential for improving patient outcomes.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transporters is a significant challenge in cancer chemotherapy.
  • Cervical cancer cell lines exhibit resistance to conventional chemotherapeutic drugs due to ABC transporter activity.

Purpose of the Study:

  • To investigate the efficacy of rucaparib, a Poly (ADP-ribose) polymerase (PARP) inhibitor, in overcoming ABC transporter-mediated MDR in cervical cancer.
  • To evaluate rucaparib's impact on the accumulation and efflux of chemotherapeutic drugs in resistant cervical cancer cells.

Main Methods:

  • Experiments were conducted using drug-resistant cervical cancer cell lines.
  • Rucaparib's effect on drug cytotoxicity, intracellular drug accumulation, and drug efflux was assessed.
  • Molecular docking studies were performed to analyze the interaction between rucaparib and ABC transporters.

Main Results:

  • Rucaparib significantly enhanced the cytotoxic effects of conventional chemotherapeutic drugs in resistant cervical cancer cells.
  • Rucaparib increased the intracellular accumulation of rhodamine 123 and tritium-labeled chemotherapeutic drugs.
  • Rucaparib decreased the efflux of tritium-labeled chemotherapeutic drugs, indicating inhibition of ABC transporter function.
  • Molecular docking suggested rucaparib binds to the active site of ABC transporters.

Conclusions:

  • Rucaparib antagonizes MDR in cervical cancer by inhibiting the function of ABC transporters.
  • Combining rucaparib with chemotherapeutic agents may offer a promising therapeutic strategy for cervical cancer patients.
  • This study provides a rationale for clinical trials evaluating rucaparib in combination therapy for cervical cancer.
Keywords:
ABC transportersCervical Cancer (CC)Multidrug resistance (MDR)Rucaparib

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