Psoralen reverses the P-glycoprotein-mediated multidrug resistance in human breast cancer MCF-7/ADR cells

Jiang,Jingru; Wang,Xiaohong; Cheng,Kai; Zhao,Wanzhong; Hua,Yitong; Xu,Chengfeng; Yang,Zhenlin

doi:10.3892/mmr.2016.5098

Psoralen reverses the P-glycoprotein-mediated multidrug resistance in human breast cancer MCF-7/ADR cells

Authors:
- Jingru Jiang
- Xiaohong Wang
- Kai Cheng
- Wanzhong Zhao
- Yitong Hua
- Chengfeng Xu
- Zhenlin Yang
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Affiliations: Department of Thyroid and Breast Surgery, The Affiliated Hospital of Binzhou University of Medicine, Binzhou, Shandong 256603, P.R. China
Published online on: April 8, 2016 https://doi.org/10.3892/mmr.2016.5098
Pages: 4745-4750

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Abstract

The resistance of cancer to chemotherapeutic agents is a major obstacle during chemotherapy. Clinical multidrug resistance (MDR) is commonly mediated by membrane drug efflux pumps, including ATP‑binding cassette subfamily B member 1, also termed P-glycoprotein (P-gp). P-gp is a membrane transporter encoded by the MDR1 gene. The current study aimed to investigate the impact of psoralen on the expression and function of P‑gp. The 10% inhibitory concentration (IC10) of psoralen, and its capacity to reduce MDR in adriamycin (ADR)‑resistant MCF‑7/ADR cells were determined using MTT assay. The ability of psoralen to modulate the transport activity of P‑gp in MCF‑7/ADR cells was evaluated by measuring the accumulation and efflux of rhodamine 123 (Rh 123) and adriamycin with flow cytometry. The present study evaluated the mRNA level of MDR1 in MCF‑7 and MCF‑7/ADR cells treated with psoralen using reverse transcription-quantitative polymerase chain reaction. The protein expression level of P‑gp was examined by western blot analysis. The current study demonstrated that the IC10 of psoralen in MCF‑7/ADR cells was 8 µg/ml. At 8 µg/ml, psoralen reduced MDR and the sensitivity of the MCF‑7/ADR cells to ADR compared with untreated cells. Additionally, psoralen significantly increased the intracellular accumulation of ADR and Rh 123. However, the IC10 of psoralen did not affect the protein expression levels of P‑gp or mRNA levels of MDR1 (P>0.05). Psoralen reduces MDR by inhibiting the efflux function of P‑gp, which may be important for increasing the efficiency of chemotherapy and improving the clinical protocols aiming to reverse P-gp-mediated MDR.

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