Guo Jinqiu, Fan Jianhui, Zhang Yaru, Li Mengyue, Jin Zeen, Shang Yuhong, Zhang Hongshuo, Kong Ying
Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
Department of Gynecology, First Affiliated Hospital of Dalian Medical University, Dalian, China.
Biosci Rep. 2024 Mar 29;44(3). doi: 10.1042/BSR20232035.
Endometrial carcinoma (EC) is a common malignancy that originates from the endometrium and grows in the female reproductive system. Surgeries, as current treatments for cancer, however, cannot meet the fertility needs of young women patients. Thus, progesterone (P4) therapy is indispensable due to its effective temporary preservation of female fertility. Many cancer cells are often accompanied by changes in metabolic phenotypes, and abnormally dependent on the amino acid glutamine. However, whether P4 exerts an effect on EC via glutamine metabolism is unknown. In the present study, we found that P4 could inhibit glutamine metabolism in EC cells and down-regulate the expression of the glutamine transporter ASCT2. This regulation of ASCT2 affects the uptake of glutamine. Furthermore, the in vivo xenograft studies showed that P4 inhibited tumor growth and the expression of key enzymes involved in glutamine metabolism. Our study demonstrated that the direct regulation of glutamine metabolism by P4 and its anticancer effect was mediated through the inhibition of ASCT2. These results provide a mechanism underlying the effects of P4 therapy on EC from the perspective of glutamine metabolism.
子宫内膜癌（EC）是一种常见的恶性肿瘤，起源于子宫内膜并在女性生殖系统中生长。然而，作为目前癌症的治疗方法，手术无法满足年轻女性患者的生育需求。因此，孕激素（P4）治疗因其能有效暂时保留女性生育能力而不可或缺。许多癌细胞常伴有代谢表型的改变，且异常依赖氨基酸谷氨酰胺。然而，P4是否通过谷氨酰胺代谢对EC发挥作用尚不清楚。在本研究中，我们发现P4可抑制EC细胞中的谷氨酰胺代谢，并下调谷氨酰胺转运体ASCT2的表达。ASCT2的这种调节作用影响谷氨酰胺的摄取。此外，体内异种移植研究表明，P4抑制肿瘤生长以及参与谷氨酰胺代谢的关键酶的表达。我们的研究表明，P4对谷氨酰胺代谢的直接调节及其抗癌作用是通过抑制ASCT2介导的。这些结果从谷氨酰胺代谢的角度为P4治疗EC的作用机制提供了依据。
