RRC ID 68429
著者 Kashio-Yokota Y, Sato S, Hirose T, Watanabe T, Endo A, Watanabe F, Endo M, Ohba K, Mori T, Takahashi K.
タイトル Elevated (Pro)renin Receptor Expression by Anti-Cancer Drugs, Carboplatin and Paclitaxel, in Cultured Cancer Cells: Possible Involvement of Apoptosis and Autophagy.
ジャーナル Tohoku J Exp Med
Abstract (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.
巻・号 255(2)
ページ 91-104
公開日 2021-10-1
DOI 10.1620/tjem.255.91
PMID 34645770
MeSH Antineoplastic Agents / pharmacology Apoptosis* / drug effects Autophagy* / drug effects Carboplatin / pharmacology Humans Neoplasms Paclitaxel / pharmacology RNA, Messenger Renin / metabolism Renin / pharmacology Vacuolar Proton-Translocating ATPases
IF 1.441
リソース情報
ヒト・動物細胞 MCF7(RCB1904) A549(RCB3677)