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.
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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) |