ArticleCancer management and research2020
Circadian Clock Protein PERIOD2 Suppresses the PI3K/Akt Pathway and Promotes Cisplatin Sensitivity in Ovarian Cancer.
Article in Cancer management and research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Chemoresistance in Ovarian Cancer and Association with Circadian Rhythm.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- The role of circadian disruption, sleep dysregulation, lifestyle factors, and metabolic reprogramming in the pathogenesis and progression of ovarian cancer.Journal of the National Cancer Center · 2026Review
- Targeting the Golgi apparatus enhances PD-L1 blockade and synergizes with oxaliplatin to improve immunotherapy efficacy.The Journal of biological chemistry · 2026Article
- The Potential of Chronotherapy and Nanotherapy-Based Strategies for Glioblastoma Treatment.Pharmaceutics · 2026Review
- The interplay between circadian rhythm components and apoptosis in health and disease.Human cell · 2026Review
- The Circadian Modulators as Molecular Targets in Cancer-A Review.International journal of molecular sciences · 2025Review
- Reporter-Mediated Evaluation of the Circadian Oscillations ofClocks & sleep · 2025Article
- Role of the period family in mediating the interplay between circadian disruption and cancer (Review).Oncology letters · 2025Review
- Dynamic and functional analyses of exosomal miRNAs regulating cellular microenvironment of ovarian cancer cells.Journal of ovarian research · 2025Article
- The interplay between the PI3K/AKT pathway and circadian clock in physiologic and cancer-related pathologic conditions.Cell proliferation · 2024Review
- Circadian patterns of growth factor receptor-dependent signaling and implications for carcinogenesis.Cell communication and signaling : CCS · 2024Review
- Importance of Per2 in cardiac mitochondrial protection during stress.Scientific reports · 2024Article
- The role of circadian clocks in cancer: Mechanisms and clinical implications.Genes & diseases · 2023Review
- Role of Melatonin in Cancer: Effect on Clock Genes.International journal of molecular sciences · 2023Review
- Potential Role of the Circadian Clock in the Regulation of Cancer Stem Cells and Cancer Therapy.International journal of molecular sciences · 2022Review
- Obesity, cancer risk, and time-restricted eating.Cancer metastasis reviews · 2022Review
- Circadian Period 2 (Per2) downregulate inhibitor of differentiation 3 (Id3) expression via PTEN/AKT/Smad5 axis to inhibits glioma cell proliferation.Bioengineered · 2022Article
- Development and performance evaluation of TaqMan real-time fluorescence quantitative methylation specific PCR for detecting methylation level of PER2.Molecular biology reports · 2022Article
- Article
- Roles of circadian clocks in cancer pathogenesis and treatment.Experimental & molecular medicine · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe mortality rate of ovarian cancer is the highest among gynecological tumors. The two factors leading to high mortality of ovarian cancer are late clinical stage and chemotherapy resistance. It is very important to reverse or intervene chemotherapy resistance. Abnormal circadian rhythm is related to the occurrence of tumor, and circadian clock protein PERIOD2 (PER2) acts as a tumor suppressor in cancer; however, little is known about its involvement in chemosensitivity.
methodsThis study aimed to investigate the role and underlying mechanisms of PER2 in ovarian cancer sensitivity to cisplatin. Overexpression and knockdown of PER2 were performed to explore its role in ovarian cancer cell sensitivity to cisplatin both in vitro and in vivo. The protein levels of PI3K, AKT, caspase 3, E-cadherin, and other drug resistance-related molecules were determined in parental SKOV3 and SKOV3/DDP cells as well as in xenograft tumor tissues.
resultsCompared with parental cells, SKOV3/DDP cells had dramatically decreased PER2 expression, possibly due to hypermethylation in the PER2 promoter. PER2 overexpression significantly inhibited proliferation while promoting cisplatin-induced apoptosis in SKOV3 and SKOV3/DDP cells. In agreement, PER2-overexpressing SKOV3/DPP cells yielded significantly reduced tumor mass in cisplatin-treated mice compared with control cells. Mechanistically, PER2 overexpression remarkably reduced the protein amounts of PI3K, AKT, and MDR1 while increasing those of caspase 3 and E-cadherin in tumor tissues. Knockdown of PER2 exhibited opposite effects. PER2 overexpression also reduced the serum levels of TNF-α and IL-6 in tumor-bearing mice before the initiation of cisplatin treatment.
conclusionThis study suggests that loss of PER2 contributes to cisplatin resistance in SKOV3 cells, possibly by activating the PI3K/AKT pathway and EMT, inhibiting apoptosis, and promoting drug efflux and inflammatory responses. Overexpression of PER2 could reverse these alterations and sensitize both parental SKOV3 and SKOV3/DDP cells to cisplatin.
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