Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (1): 8-13.doi: 10.6040/j.issn.1671-7554.0.2020.1297

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CDK7 inhibitor THZ1 increases the radiosensitivity of human glioma cell line U251

LI Wenqing, YE Lan, JIANG Yuhua   

  1. Cancer Prevention and Control Center, The Second Hospital of Shandong University, Jinan 250031, Shandong, China
  • Published:2021-01-09

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Abstract: Objective To investigate the effects of cyclin-dependent kinase 7(CDK7)inhibitor, THZ1, on the radiosensitivity of human glioma cell line U251 in vitro. Methods U251 cells were cultured in vitro. The toxic effects of THZ1 on U251 cells was detected with MTT. The cell survival curves were drawn at different concentrations of THZ1(0, 8, 16, 32, 64, 128, 256, 512 noml/L). IC50 and IC20 were calculated and IC20 was used as the concentration for subsequent experiments. The effects of X-ray combined with THZ1 on U251 was detected with clone formation experiment. Radiosensitivity parameters were calculated and the curve of colony formation number was drawn. Cell cycle distribution in each treatment group was detected with flow cytometry. The expressions of CDK7 cyclin, Bax apoptosis-related proteins and γH2AX were detected with Western blotting. One-factor analysis of variance was used for comparison among groups. Independent sample t test was used for comparison between groups. Factorial design analysis of variance was used for two-factor comparison among groups. Results THZ1 inhibited U251 proliferation in a concentration- and time-dependent manner. THZ1 inhibited CDK7 cyclin. X-ray(6 Gy)combined with IC20 concentration of THZ1(10 nmol/L)reduced the cloning ability of U251(the ratio of enhancing sensitivity being 1.478), decreased the percentage of G0/G1 phase from 67% to 11%, increased the percentage of G2/M phase from 12% to 70%, and increased the expressions of Bax apoptosis-related proteins and γH2AX. Conclusion THZ1 can increase the radiosensitivity of U251. The possible mechanism is that THZ1 combined with X-ray inhibits the repair ability of cells, induces cell apoptosis, regulates expressions of apoptosis-related proteins, and intervenes in the cell cycle.

Key words: Human glioma cell U251, Radiosensitivity, Proliferation, Cell cycle

CLC Number: 

  • R739.41
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