High Expression of p21 as a Potential Therapeutic Target in Ovarian Clear-cell Carcinoma

Minagawa, Yuki; Ishino, Kousuke; Wada, Ryuichi; Kudo, Mitsuhiro; Naito, Zenya; Takeshita, Toshiyuki; Ohashi, Ryuji

doi:10.21873/anticanres.14576

Cited by 2 publications

(2 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, higher concentrations of doxorubicin (1 µM) have been shown to induce p21 in NB cell lines ( 45 ), suggesting that the induction of p21 might be concentration dependent. Moreover, an increase in either the fraction or the mean intensity of p-p21 positive cells was observed in three of the four tested cell lines, Kelly, SK-N-DZ, and BE(2)-C, indicating a preference for the anti-apoptotic function of p-p21 over its cell cycle regulatory function in NB cells, similar to findings in clear-cell carcinomas, testicular cancer, and ovarian cancer treated with cisplatin ( 11 , 12 , 46 ).…”

Section: Discussionsupporting

confidence: 70%

The cyclin dependent kinase inhibitor p21Cip1/Waf1 is a therapeutic target in high-risk neuroblastoma

et al. 2022

View full text Add to dashboard Cite

Platinum-based chemotherapies such as cisplatin are used as first-line treatment for the paediatric tumour neuroblastoma. Although the majority of neuroblastoma tumours respond to therapy, there is a high fraction of high-risk neuroblastoma patients that eventually relapse with increased resistance. Here, we show that one key determinant of cisplatin sensitivity is phosphorylation of the cyclin-dependent kinase inhibitor p21Cip1/Waf1. A panel of eight neuroblastoma cell lines and a TH-MYCN mouse model were investigated for the expression of p21Cip1/Waf1 using RT-qPCR, Western blot, and immunofluorescence. This was followed by investigation of sensitivity towards cisplatin and the p21Cip1/Waf1 inhibitor UC2288. Whereas the cell lines and the mouse model showed low levels of un-phosphorylated p21Cip1/Waf1, the phosphorylated p21Cip1/Waf1 (Thr145) was highly expressed, which in the cell lines correlated to cisplatin resistance. Furthermore, the neuroblastoma cell lines showed high sensitivity to UC2288, and combination treatment with cisplatin resulted in considerably decreased cell viability and delay in regrowth in the two most resistant cell lines, SK-N-DZ and BE(2)-C. Thus, targeting p21Cip1/Waf1 can offer new treatment strategies and subsequently lead to the design of more efficient combination treatments for high-risk neuroblastoma.

show abstract

Section: Discussionsupporting

confidence: 70%

The cyclin dependent kinase inhibitor p21Cip1/Waf1 is a therapeutic target in high-risk neuroblastoma

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Yan et al discovered that inhibiting p21 in QGP-1 and NCI-H727 cells by treatment with UC2288, further enhanced the cytotoxicity of artesunate, implying that p21 may confer resistance to artesunate on these two cell lines ( 38 ). In addition, p21 inhibitor-induced death in cells with high p21 expression suggests that p21 suppression could be a therapeutic strategy for patients with clear cell carcinoma ( 39 ). Although the present research has certain limitations, such as only conducting experiments on a few cell lines and lacking evidence from in vivo experiments, it still suggests that p21 may be a new marker of drug resistance, and that p21 suppression could be a therapeutic strategy for patients with cancer.…”

Section: Discussionmentioning

confidence: 99%

p21 promotes gemcitabine tolerance in A549 cells by inhibiting DNA damage and altering the cell cycle

Fu,

Ma,

et al. 2023

Oncol Lett

View full text Add to dashboard Cite

Gemcitabine is one of the most widely used chemotherapy drugs for advanced malignant tumors, including non-small cell lung cancer. However, the clinical efficacy of gemcitabine is limited due to drug resistance. The aim of the present study was to investigate the role of p21 in gemcitabine-resistant A549 (A549/G + ) lung cancer cells. IC 50 values were determined using a Cell Counting Kit-8 (CCK-8) assay. mRNA and protein expression levels of genes were measured by reverse transcription-quantitative PCR and western blotting, respectively. The cell cycle distribution and apoptosis rate were analyzed by flow cytometry. DNA damage in cells was evaluated by single-cell gel electrophoresis. The results of western blot analysis and the CCK-8 assay demonstrated that the expression of p21 was higher in A549/G + cells than in gemcitabine-sensitive cells. Knockdown of p21 expression in gemcitabine-resistant cells sensitized these cells to gemcitabine (with the IC 50 decreasing from 84.2 to 26.7 µM). Cell cycle analysis revealed different changes in the cell cycle distribution in A549/G + cells treated with the same concentration of gemcitabine, and decreased expression of p21 was shown to promote G 1 arrest. The apoptosis assay and comet assay results revealed that decreased p21 expression resulted in accumulation of unrepaired DNA double-strand breaks (DSBs) and induction of apoptosis by gemcitabine. The present study demonstrated that knockout of p21 mRNA expression in A549/G + cells promotes apoptosis and DNA DSB accumulation, accompanied by G 1 arrest. These results indicated that p21 is involved in regulating the response of A549 cells to gemcitabine.

show abstract

High Expression of p21 as a Potential Therapeutic Target in Ovarian Clear-cell Carcinoma

Cited by 2 publications

References 24 publications

The cyclin dependent kinase inhibitor p21Cip1/Waf1 is a therapeutic target in high-risk neuroblastoma

The cyclin dependent kinase inhibitor p21Cip1/Waf1 is a therapeutic target in high-risk neuroblastoma

p21 promotes gemcitabine tolerance in A549 cells by inhibiting DNA damage and altering the cell cycle

Contact Info

Product

Resources

About