谷氨酰胺合成酶GS通过增强抗凋亡能力降低TNBC细胞对紫杉醇的敏感性

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Abstract Objective Triple-negative breast cancer (TNBC) is characterized by strong drug resistance. So patients will be less sensitive to paclitaxel, which is the most commonly used chemotherapeutic drug in the clinic, resulting in poor treatment efficacy. Glutamine Synthetase (GS) is a key metabolic enzyme needed to synthesize glutamine, and its high expression can induce ovarian cancer cells to reduce their sensitivity to chemotherapeutic drugs. However, whether GS affects the sensitivity of TNBC cells to paclitaxel and its possible mechanism are still unclear. The purpose of this study was to investigate whether GS affects the sensitivity of TNBC cells to paclitaxel and its mechanism. Methods TNBC cell lines overexpressing and knocking down GS were constructed by plasmid transfection and lentivirus infection, respectively. The effect of GS on paclitaxel sensitivity in TNBC cells was analyzed by Western blot analysis, cell viability assay, colony formation assay and apoptosis detection. qRT-PCR was used to detect the expression of drug metabolic enzymes, drug transporters, and anti-apoptotic proteins in cells overexpressing GS. Results GS was highly expressed in breast cancer cells. The sensitivity of GS^low cells (MDA-MB-231) to paclitaxel was higher than that of GS^high cells (MDA-MB-468). Overexpression of GS decreased the sensitivity of TNBC cells to paclitaxel, enhanced the ability of clone formation and anti-apoptosis, knocking down GS could increase the killing effect of paclitaxel on TNBC cells, and the expression of anti-apoptotic protein BAG3 was significantly increased in TNBC cells overexpressing GS. Conclusions In TNBC cells, the overexpression of GS promotes cell proliferation, reduces apoptosis, and enhances the ability of clone formation in TNBC cells. The anti-apoptotic effect of GS was mediated by up-regulating the expression of BAG3, thus reducing the sensitivity of TNBC cells to paclitaxel.

Key words： triple negative breast cancer glutamine synthetase paclitaxel drug sensitivity

Received: 16 May 2023

PACS:

R737.9

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	Articles by authors
	ZHU Jianyu
	XIA Hongzhuo
	ZHENG Zhuomeng
	PENG Xiaoning
	DENG Xiyun
	FU Shujun

Cite this article:

ZHU Jianyu,XIA Hongzhuo,ZHENG Zhuomeng等. Glutamine Synthetase reduces the sensitivity of TNBC cells to paclitaxel by enhancing anti-apoptosis ability[J]. HuNan ShiFan DaXue XueBao(YiXueBan), 2023, 20(3): 10-15.

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http://yxb.hunnu.edu.cn/EN/ OR http://yxb.hunnu.edu.cn/EN/Y2023/V20/I3/10

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