Abstract | OBJECTIVE: METHODS:
Ovarian cancer SKOV3 cells cultured in vitro were treated with different concentrations of DDP (1-20 μg/mL). MTT assay was used to observe the changes in proliferation of the treated cells and the effect of treatment with 100 ng/mL IL-17A for 24 h on DDP-induced apoptosis of SKOV3 cells. We then examined the expression of IL-17A receptor (IL-17RA) in SKOV3 cells using flow cytometry. Annexin V-FITC/PI double staining was used to detect the cell apoptosis rate, and early apoptosis of the cells was detected with JC-1 assay. A neutralizing monoclonal antibody (mAb) against IL-17RA was used to block IL-17RA. We also observed the effects of IL-17RA silencing mediated by a siRNA targeting IL-17RA (siRNA-IL-17RA) and treatment with 3-methyladenine (3-MA) for inhibiting autophagy on DDP-induced apoptosis of SKOV3 cells. The expressions of apoptosis-related proteins (Bcl-2, Bax, and cleaved caspase-3) and autophagy-related proteins (P62 and Beclin-1) in the treated cells were detected using Western blotting. RESULTS: DDP increased the expression of IL-17RA in ovarian cancer SKOV3 cells. Treatment with IL-17A significantly reduced the susceptibility of SKOV3 cells to cisplatin-induced apoptosis (P < 0.05). DDP obviously augmented the expression of Beclin-1 and reduced the autophagy degradation substrate P62 protein in the cells (P < 0.05). IL-17A/IL-17RA strongly enhanced the DDPinducted autophagy of the cells (P < 0.05). Blocking autophagy with 3-MA significantly increased DDP- induced apoptosis of SKOV3 cells with IL-17RA silencing, lowered the expression of Bcl-2 and enhanced Bax expression in the cells (P < 0.05). CONCLUSIONS: IL-17A/IL-17RA can decrease chemosensitivity of SKOV3 cells to DDP by upregulating DDP-induced autophagy.
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Authors | Lihua Wang, Xuan Zhang, Liangliang Wang, Beibei Wang, Jing Zhang, Yuzhi Li |
Journal | Nan fang yi ke da xue xue bao = Journal of Southern Medical University
(Nan Fang Yi Ke Da Xue Xue Bao)
Vol. 40
Issue 11
Pg. 1550-1556
(Nov 30 2020)
ISSN: 1673-4254 [Print] China |
PMID | 33243748
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- IL17RA protein, human
- Interleukin-17
- Receptors, Interleukin-17
- Cisplatin
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Topics |
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Apoptosis
(drug effects)
- Autophagy
(drug effects)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cisplatin
(pharmacology)
- Drug Resistance, Neoplasm
(drug effects)
- Female
- Humans
- Interleukin-17
(pharmacology)
- Ovarian Neoplasms
(drug therapy)
- Receptors, Interleukin-17
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