Elevated (Pro)renin Receptor Expression by Anti-Cancer Drugs, Carboplatin and Paclitaxel, in Cultured Cancer Cells: Possible Involvement of Apoptosis and Autophagy
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- Kashio-Yokota Yurina
- Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine
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- Sato Shigemitsu
- Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine
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- Hirose Takuo
- Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine Division of Nephrology and Endocrinology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University Division of Integrative Renal Replacement Therapy, Faculty of Medicine, Tohoku Medical and Pharmaceutical University
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- Watanabe Tomoki
- Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine
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- Endo Akari
- Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine Division of Nephrology and Endocrinology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University
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- Watanabe Fumihiko
- Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine
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- Endo Moe
- Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine
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- Ohba Koji
- Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine
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- Mori Takefumi
- Division of Nephrology and Endocrinology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University Division of Integrative Renal Replacement Therapy, Faculty of Medicine, Tohoku Medical and Pharmaceutical University
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- Takahashi Kazuhiro
- Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine
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Abstract
<p>(Pro)renin receptor [(P)RR] is a component of the renin-angiotensin system and plays an essential role in the activity of vacuolar H+-ATPase and autophagy. (P)RR is expressed in cancer cells. However, the relationship among (P)RR, apoptosis and autophagy in the treatment of anti-cancer drugs has not been clarified. The aim of this study was to clarify the effects of anti-cancer drugs with autophagy-promoting activity on (P)RR expression in cancer cells. MCF-7 breast cancer cells and A549 lung cancer cells were treated with carboplatin or paclitaxel, and the expression of (P)RR, apoptosis markers and autophagy markers were assessed by RT-qPCR, western blot analysis and immunocytochemistry. Expression levels of (P)RR mRNA and soluble (P)RR protein were increased by carboplatin or paclitaxel in a dose-dependent manner. Immunofluorescence staining of (P)RR was increased in both MCF-7 and A549 cells treated by carboplatin or paclitaxel. Apoptosis induction was shown by elevated BAX/BCL2 mRNA levels and increased active caspase3-positive cells. Moreover, autophagy induction was confirmed by increased levels of autophagy-associated mRNAs and LC3B-II proteins. (P)RR knockdown by (P)RR-specific siRNA suppressed the cell viability in MCF-7 cells and A549 cells under the treatment of carboplatin or paclitaxel, suggesting that (P)RR deficiency inhibits the proliferation of cancer cells in a pathway different from carboplatin or paclitaxel. The present study showed that the expression of (P)RR mRNA and soluble (P)RR was increased by anti-cancer drugs with autophagy-promoting activity. Upregulated (P)RR and autophagy may constitute a stress adaptation that protects cancer cells from apoptosis.</p>
Journal
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- The Tohoku Journal of Experimental Medicine
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The Tohoku Journal of Experimental Medicine 255 (2), 91-104, 2021
Tohoku University Medical Press