KW-2478对结直肠癌细胞增殖的抑制作用及其机制

doi:10.3969/j.issn.1004-616x.2024.03.006

Abstract

Abstract: OBJECTIVE：To investigate effect and underlying mechanism of HSP90α inhibitor KW-2478 on malignant phenotypes of colorectal cancer (CRC) cells. METHODS：Using DMSO as solvent control，colorectal cancer cells RKO and DLD1 were treated with different concentrations of KW-2478. The proliferation rate of colorectal cancer cells was detected by CCK8 kit；the colony formation rate was detected by plate colony formation assay；flow cytometry was used to analyze the cell cycle；Western blot was used to detect the expression level and phosphorylation level of proliferation and cycle regulation-related proteins. RESULTS：Compared with the control group，the proliferation capacity of RKO cells treated with 0.8 μmol/L KW-2478 and DLD1 cells treated with 40 μmol/L KW-2478 decreased by more than 50%，and the IC₅₀ of both cells were (0.5±1.2) μmol/L and (40.0±3.1) μmol/L，respectively. After treatment with KW-2478，the sum colony formation rate of both cells were reduced by more than 40% when compared with the control group (P<0.01) . Meanwhile，KW-2478 significantly induced G2/M phase arrest (P<0.01). Upon KW-2478 treatment，the protein abundance of HSP90a client proteins EGFR，AKT and S6，and the phosphorylation levels of AKT，ERK and S6 were reduced，while the expressions of mitosis-specific marker p-Histone H3 and Cyclin B1 protein were upregulated. CONCLUSION：KW-2478 significantly inhibited the proliferation viability and colony formation ability of RKO and DLD1 and induced markedly G2/M phase arrest. The observed effects may be related to inhibiting the activity of EGFR-related signaling pathways and upregulating the expression of cycle-related proteins.

Key words: colorectal cancer, HSP90, KW-2478, proliferation, cell cycle, EGFR

CLC Number:

R735.1

XIAO Xue, LU Xiaotong, CHEN Siqi, JIANG Yujuan, HAO Jiajie, CAI Yan, WANG Mingrong, ZHANG Yu. Inhibitory effect and underlying mechanism of KW-2478 on proliferation of colorectal cancer cells in vitro[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2024, 36(3): 202-207.

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Inhibitory effect and underlying mechanism of KW-2478 on proliferation of colorectal cancer cells in vitro

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