精准医学杂志 (Jun 2023)

EFFECT OF A NOVEL HEAT SHOCK PROTEIN 90/HISTONE DEACETYLASE DUAL-TARGET INHIBITOR ON THE PROLIFE-RATION, INVASION, AND MIGRATION OF BREAST CANCER MDA-MB-231 CELLS AND ITS MECHANISM

  • GAO Xiao, WU Qinglan, DENG Lin, SONG Junying, ZHANG Li, LUAN Yepeng, ZHANG Jinping, HOU Lin

DOI
https://doi.org/10.13362/j.jpmed.202303014
Journal volume & issue
Vol. 38, no. 3
pp. 249 – 253

Abstract

Read online

Objective To investigate the effect of FXX-W-12-4, a novel heat shock protein 90 (Hsp90)/histone deacetylase (HDAC) dual-target inhibitor, on the proliferation, invasion, and migration of breast cancer MDA-MB-231 cells. Methods CCK-8 assay was used to observe the effect of FXX-W-12-4 on the viability of MDA-MB-231 cells, and its half-maximal inhibitory concentration (IC50) was calculated as the reference value for concentration in follow-up experiment. On the basis of the IC50 value, FXX-W-12-4 with a final concentration of 0, 100, 200, and 300 nmol/L was added to MDA-MB-231 cells and was established as groups A, B, C, and D, respectively. Cell scratch assay and Transwell assay were used to observe the effect of FXX-W-12-4 on the invasion and migration of MDA-MB-231 cells in each group. Western blot was used to measure the relative expression levels of proteins such as ac-H3 and Hsp70 in MDA-MB-231 cells. Results CCK-8 assay showed that the viability of MDA-MB-231 cells gradually decreased with the increase in FXX-W-12-4 concentration (F=2 663.00,P<0.05). Cell scratch assay showed that compared with group A, groups B, C, and D had a significant reduction in the migration ability of MDA-MB-231 cells at 12, 24, and 48 h (F=86.47-212.59,P<0.05). Transwell assay showed that compared with group A, groups B, C, and D showed a significant reduction in the invasion ability of MDA-MB-231 cells with the increase in FXX-W-12-4 concentration (F=68.67,P<0.05). Western blot showed that compared with group A, groups B, C, and D showed significant increases in the relative protein expression levels of ac-H3 and Hsp70 (F=645.60,1 017.00,P<0.05) and significant reductions in the protein expression levels of p-Akt and p-mTOR (F=480.30,14.32,P<0.05) with the increase in FXX-W-12-4 concentration. Conclusion The novel Hsp90/HDAC dual-target inhibitor FXX-W-12-4 can effectively inhibit the proliferation, invasion, and migration of breast cancer MDA-MB-231 cells, possibly by regulating the Akt/mTOR pathway.

Keywords