Decreased sensitivity of several anticancer drugs in TMEPAI knockout triple-negative breast cancer cells

  • Bantari Wisynu Kusuma Wardhani Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Meidi Utami Puteri Medical Science Master Program, Graduate School of Comprehensive Human Science, University of Tsukuba, Ibaraki, Japan
  • Yukihide Watanabe Department of Experimental Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
  • Melva Louisa Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Rianto Setiabudy Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Mitsuyasu Kato Department of Experimental Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
Keywords: BCRP, MRP1, P-glycoprotein, TMEPAI, triple-negative breast cancer cell
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Abstract

BACKGROUND Transmembrane prostate androgen-induced protein (TMEPAI) was reported to be highly amplified in the majority of patients with triple-negative breast cancer (TNBC). TMEPAI is related to poorer prognosis, limited treatment options, and prone to drug resistance compared with other proteins. One of the established markers to determine cancer resistance to drugs is the increased expression levels of drug efflux transporters. However, the role of TMEPAI in cancer resistance to drugs has not been elucidated. This study was aimed to investigate whether TMEPAI participates in cancer resistance to drugs by regulating drug efflux transporters.

METHODS TMEPAI knockout (KO) cells were previously developed from a TNBC cell line, Hs578T (wild-type/WT), using a CRISPR-Cas9 system. The expression levels of drug efflux transporters were determined in Hs578T-KO and Hs578-WT by quantitative reverse transcriptase polymerase chain reaction. Cytotoxic concentration 50% (CC50) of several anticancer drugs (doxorubicin, cisplatin, and paclitaxel) were determined in the two cell lines via 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay.

RESULTS The results showed that the mRNA expression of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) was significantly increased in Hs578T-KO compared with that in Hs578T-WT cells. CC50 of several anticancer drugs investigated (doxorubicin, paclitaxel, and cisplatin) in Hs578T-KO cells was higher than that in Hs678-WT.

CONCLUSIONS TMEPAI participated in the regulation of mRNA expression levels in drug efflux transporters (P-gp, BCRP, and multidrug resistance-associated protein 1). Further studies are necessary to confirm whether this finding might be dependent on the development of cancer cell sensitivity to anticancer agents.

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Published
2019-08-09
How to Cite
1.
Wardhani BWK, Puteri MU, Watanabe Y, Louisa M, Setiabudy R, Kato M. Decreased sensitivity of several anticancer drugs in TMEPAI knockout triple-negative breast cancer cells. Med J Indones [Internet]. 2019Aug.9 [cited 2019Aug.18];28(2):110-5. Available from: https://mji.ui.ac.id/journal/index.php/mji/article/view/2687
Section
Basic Medical Research