WEE1 inhibition enhances sensitivity to hypoxia/reoxygenation in HeLa cells

Goto, Tatsuaki; Homma, Hisao; Kaida, Atsushi; Miura, Masahiko

doi:10.1093/jrr/rrz045

Cited by 2 publications

(2 citation statements)

References 14 publications

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“…Colony formation assay was performed as described previously 34 . To determine HeLa-Fucci (CA)2 radiosensitivity, an appropriate number of cells were seeded in 60-mm dishes in triplicate and immediately irradiated.…”

Section: Methodsmentioning

confidence: 99%

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Fluctuation in radioresponse of HeLa cells during the cell cycle evaluated based on micronucleus frequency

Shimono

Kaida

Homma

et al. 2020

Sci Rep

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In this study, we examined the fluctuation in radioresponse of HeLa cells during the cell cycle. For this purpose, we used HeLa cells expressing two types of fluorescent ubiquitination-based cell cycle indicators (Fucci), HeLa-Fucci (CA)2 and HeLa-Fucci (SA), and combined this approach with the micronucleus (MN) assay to assess radioresponse. The Fucci system distinguishes cell cycle phases based on the colour of fluorescence and cell morphology under live conditions. Time-lapse imaging allowed us to further identify sub-positions within the G1 and S phases at the time of irradiation by two independent means, and to quantitate the number of MNs by following each cell through M phase until the next G1 phase. Notably, we found that radioresponse was low in late G1 phase, but rapidly increased in early S phase. It then decreased until late S phase and increased in G2 phase. For the first time, we demonstrated the unique fluctuation of radioresponse by the MN assay during the cell cycle in HeLa cells. We discuss the difference between previous clonogenic experiments using M phase-synchronised cell populations and ours, as well as the clinical implications of the present findings.

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Section: Methodsmentioning

confidence: 99%

“…Statistical analyses were performed as described previously 33 , 34 . Mann–Whitney U test, one-way ANOVA with post hoc Tukey's multiple comparison test, Student’s t-test, or chi‐square test was used as appropriate.…”

Section: Methodsmentioning

confidence: 99%

Fluctuation in radioresponse of HeLa cells during the cell cycle evaluated based on micronucleus frequency

Shimono

Kaida

Homma

et al. 2020

Sci Rep

Self Cite

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WEE1 Inhibitor Adavosertib Exerts Antitumor Effects on Colorectal Cancer, Especially in Cases with p53 Mutations

Ariyoshi,

Yuge,

Kitadai

et al. 2024

Cancers

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Inhibition of WEE1, a key regulator of the G2/M checkpoint of the cell cycle, induces apoptosis by initiating mitosis without repairing DNA damage. However, the effects of WEE1 inhibitors on the tumor immune microenvironment in colorectal cancer (CRC) remain unclear. Here, we investigated the association between WEE1 expression and CRC clinicopathological features using surgically resected CRC specimens and assessed the antitumor effects of a WEE1 inhibitor using CRC cell lines and orthotopic transplantation mouse models. WEE1 expression was not correlated with the clinicopathological features of CRC. The WEE1 inhibitor suppressed cell proliferation in a concentration-dependent manner in all CRC cell lines. It also increased the percentage of cells in the G2/M phase and apoptotic cells, especially in cell lines with p53 mutations, but did not alter these cell percentages in most p53 wild-type cell lines. In the orthotopic mouse model of CRC, tumor volume was significantly reduced in the WEE1 inhibitor-treated group compared to that in the control group. RNA sequencing and immunohistochemistry analyses of mouse tumors revealed that treatment with the WEE1 inhibitor activated tumor immunity and suppressed stromal reactions. These results demonstrate the potential antitumor effects of WEE1 inhibitors in CRC, particularly in patients with p53 mutations.

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WEE1 inhibition enhances sensitivity to hypoxia/reoxygenation in HeLa cells

Cited by 2 publications

References 14 publications

Fluctuation in radioresponse of HeLa cells during the cell cycle evaluated based on micronucleus frequency

Fluctuation in radioresponse of HeLa cells during the cell cycle evaluated based on micronucleus frequency

WEE1 Inhibitor Adavosertib Exerts Antitumor Effects on Colorectal Cancer, Especially in Cases with p53 Mutations

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