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Multidrug transporters P-GP, MRP1, and ABCG2 in chemoresistant breast and colorectal cancer cells—who takes the lead?

Sudipta Deb Nath, Md. Mahmudul Hasan Akash, Md Tamzid Hossain Tanim, Sharif Akhteruzzaman, Mohammad Golam Mostafa, Abu Ashfaqur Sajib.



Abstract
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Despite significant advances in the discovery and efficacy of anticancer drugs, chemoresistance remains a major issue in cancer treatment and management. Hyperactivity of efflux pumps is one of the key mechanisms through which cancer cells acquire chemoresistance. This study investigates the expression patterns of P-GP, MRP1, and ABCG2 in 49 paired chemoresistant breast and colorectal cancer tissues using immunofluorescence imaging and statistical applications. Among breast cancer patients, 92.86% were diagnosed with infiltrating ductal carcinoma, whereas in the case of colorectal cancer, 100% had adenocarcinoma. Our immunofluorescence data show concurrent expression of ABCG2, MRP1, and P-GP across all chemoresistant breast and colorectal cases, suggesting a synergistic action of these transporters in developing chemoresistance, although the expression level varied for the transporters. Expression of ABCG2 exceeded P-GP and MRP1 expression in most cases. We suggest that a combinative and targeted therapeutic approach may be beneficial to improve the prognosis of cases with chemoresistance.

Key words: Chemoresistance; P-GP; MRP1; ABCG2; ABC transporter







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