Study of the Mechanism by Which Dinaciclib Induces Apoptosis and Cell Cycle Arrest of Lymphoma Raji Cells Through a CDK1-involved Pathway

Overview

Journal Cancer Med

Specialty Oncology

Date 2019 Jun 18

PMID 31207099

Citations 13

Authors

Huayan Zhao

Shenglei Li

Guannan Wang

Wugan Zhao

Dandan Zhang

Fang Wang

Wencai Li

Ling Sun

Affiliations

Soon will be listed here.

Abstract

Objective: This study aimed to identify and evaluate the mechanism by which apoptosis and cell cycle arrest were induced by dinaciclib in lymphoma Raji cells.

Methods: The colony formation assay was used to detect cell proliferation of Raji cells. Cell cycle arrest and cell apoptosis were determined by flow cytometry and TUNEL assays, respectively. Protein expression related to the Raji cell state was evaluated by Western blot. The Raji/Dinaciclib drug-resistant cell line was established, where the regulating functions of CDK1-involved pathway were verified. In addition, the effect of dinaciclib in vivo was examined in orthotopically implanted tumors in nude mice.

Results: Cell apoptosis was induced, and DNA synthesis ability was decreased in a time-dependent manner in dinaciclib-treated lymphoma Raji cells. Furthermore, the cell cycle was found to be blocked in the G2/M Phase. Further study indicated that CDK1-involved pathway played a key regulatory role in this process. It was revealed by cell transfection that the expression of cell cycle proteins was downregulated after treatment with dinaciclib through a CDK1-involved pathway, which eventually led to apoptosis. Knockdown of CDK1 restored the sensitivity of the Raji/Dinaciclib cells to dinaciclib. Xenograft model of nude mice showed that dinaciclib treatment in vivo could effectively inhibit tumor growth, consistent with the experiment results mentioned before.

Conclusion: In this study, we clarified the mechanisms through which dinaciclib induces Raji cell apoptosis and blocks the cell cycle through a CDK1-involved pathway, which supported that dinaciclib had potential values in the treatment of lymphoma.

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