<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec><h3>Background</h3>
<p>Non-small cell lung cancer (NSCLC) has a poor prognosis and usually presents resistance against radiotherapy. MEK inhibitors have been proven to possess a radiosensitization effect. The compound KZ-001 as a particular MEK inhibitor is superior to the listed MEK inhibitor AZD6244.</p>
</sec>
<sec><h3>Objective</h3>
<p>To investigate whether KZ-001 could enhance the radiosensitivity of NSCLC cell lines in vitro.</p>
</sec>
<sec><h3>Methods</h3>
<p>MTT and colony formation assay were used to evaluate the radiosensitivity effect of KZ-001. Immunofluorescence, cell cycle, apoptosis staining, and western blot experiments were used to explore the radiosensitivity mechanism.</p>
</sec>
<sec><h3>Results</h3>
<p>KZ-001 significantly decreased A549 cell viability at 6 Gy and 8 Gy radiation doses and caused the radiosensitivity at 1 Gy, 4 Gy, and 6 Gy in colony formation experiments. The A549 apoptosis ratio induced by irradiation (IR) combined with KZ-001 increased significantly in comparison with that by IR monotherapy (10.57% vs. 6.23%, <italic>P</italic> = 0.0055). The anti-apoptosis marker Bcl-XL was found downregulated in KZ-001 and IR-treated A549/H460 cells, but apoptosis marker Bax was downregulated in H460. Extracellular regulated protein kinases (ERK1/2) phosphorylation of H460 cells could be blocked both by IR alone and IR combined with KZ-001. IR combined with KZ-001 is able to inhibit ERK activation of A549 cells apparently. KZ-001 increased the proportion of G2 phase in irradiated cells from 21.24% to 32.22%. KZ-001 could also significantly increase the double-strand break damage cell ratio to more than 30% compared to the irradiation alone group.</p>
</sec>
<sec><h3>Conclusions</h3>
<p>MEK1/2 inhibitor KZ-001 is a potential radiosensitizer for clinical applications.</p>
</sec>
</abstract>

Background
Non-small cell lung cancer (NSCLC) has a poor prognosis and usually presents resistance against radiotherapy. MEK inhibitors have been proven to possess a radiosensitization effect. The compound KZ-001 as a particular MEK inhibitor is superior to the listed MEK inhibitor AZD6244.

Objective
To investigate whether KZ-001 could enhance the radiosensitivity of NSCLC cell lines in vitro.

Methods
MTT and colony formation assay were used to evaluate the radiosensitivity effect of KZ-001. Immunofluorescence, cell cycle, apoptosis staining, and western blot experiments were used to explore the radiosensitivity mechanism.

Results
KZ-001 significantly decreased A549 cell viability at 6 Gy and 8 Gy radiation doses and caused the radiosensitivity at 1 Gy, 4 Gy, and 6 Gy in colony formation experiments. The A549 apoptosis ratio induced by irradiation (IR) combined with KZ-001 increased significantly in comparison with that by IR monotherapy (10.57% vs. 6.23%, P = 0.0055). The anti-apoptosis marker Bcl-XL was found downregulated in KZ-001 and IR-treated A549/H460 cells, but apoptosis marker Bax was downregulated in H460. Extracellular regulated protein kinases (ERK1/2) phosphorylation of H460 cells could be blocked both by IR alone and IR combined with KZ-001. IR combined with KZ-001 is able to inhibit ERK activation of A549 cells apparently. KZ-001 increased the proportion of G2 phase in irradiated cells from 21.24% to 32.22%. KZ-001 could also significantly increase the double-strand break damage cell ratio to more than 30% compared to the irradiation alone group.

Conclusions
MEK1/2 inhibitor KZ-001 is a potential radiosensitizer for clinical applications.

Evaluation of the radiosensitizing effect of MEK inhibitor KZ-001 on non-small cell lung cancer cells in vitro

Department of Chemistry, School of Science

Asian Biomedicine

This work is licensed under the Creative Commons Attribution 4.0 International License.

Background
Non-small cell lung cancer (NSCLC) has a poor prognosis and usually presents resistance against radiotherapy. MEK inhibitors have been proven to...

Evaluation of the radiosensitizing effect of MEK inhibitor KZ-001 on non-small cell lung cancer cells in vitro

Article Category: Original article

Published Online: Oct 26, 2023

Page range: 230 - 237

DOI: https://doi.org/10.2478/abm-2023-0064

Keywords
apoptosis, DNA damage, MEK inhibitor, non-small cell lung cancer, radiosensitization

© 2023 Gongchao Huang et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Evaluation of the radiosensitizing effect of MEK inhibitor KZ-001 on non-small cell lung cancer cells in vitro

Article Category: Original article

Published Online: Oct 26, 2023

Page range: 230 - 237

DOI: https://doi.org/10.2478/abm-2023-0064

Keywordsapoptosis, DNA damage, MEK inhibitor, non-small cell lung cancer, radiosensitization

© 2023 Gongchao Huang et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Keywords
apoptosis, DNA damage, MEK inhibitor, non-small cell lung cancer, radiosensitization