Effect of X-ray irradiation on expression of organic anion transporting polypeptides

Abstract

Purpose: Some members of the organic anion transporting polypeptide (OATP) family may play critical roles in determining the concentration of anticancer drugs in targeted organs/cells. The purpose of the present study was to investigate whether radiation can alter the expression of OATP in cancer cells so that OATP can be used as a specific drug target for anti-tumor treatment in combination with radiotherapy.

Materials and methods: Two cancer cell lines (HepG2 and MCF7) were irradiated with three doses of X-ray and the expression levels of six OATP were assessed.

Results: Expressions of several OATP were altered after irradiation. OATP1A2, an OATP that was found to transport anti-tumor drugs and was undetectable in untreated cells, showed dramatically elevated level of expression after irradiation in MCF7 cells. The combined treatment of X-rays and the OATP1A2 substrate methotrexate exerted a more significant effect on growth rate and cell death compared with radiation or methotrexate treatment alone. At certain time points, X-rays increased OATP1A2 level while suppressing the expression of efflux transporters.

Conclusions: Radiation may simultaneously increase the expression of uptake transporters and decrease the level of efflux transporters, suggesting OATP may be considered a novel target for delivery of anti-neoplastic agents in combination with radiotherapy.

Keywords::

• Organic anion transporting polypeptide
• X-ray irradiation
• chemotherapy

Acknowledgements

We thank Dr Burong Hu for his kind help on the irradiation experiments.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported in part by Guangdong Province Talent Introduction Project Grant (2009) to M. Hong.