姜黄素调控子宫内膜癌细胞糖酵解过程的机制

doi:10.3969/j.issn.2095-9400.2019.12.005

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Abstract Objective: To detect the energy metabolic pathway of curcumin combined with 5-Fluorouridine and its killing effect on endometrial cancer cells. Methods: The levels of glycolysis and oxidative phosphorylation in endometrial cancer cells were measured by Seahores and Lactate/Pyruvate assay kit to confirm the main metabolic pathway in the endometrial cancer cells. Metabolic genes in Ishikawa and curcumin treated Ishikawa cells were screened by real-time PCR to explore the candidate target gene of curcumin; the level of glycolysis and oxidative phosphorylation were detected by Seahorse and the lactate/pyruvate assay in PDK2-knockout cells to reveal how curcumin regulated the energy metabolic pathway in endometrial carcinoma cells via PDK2. We establish human endometrial cancer model in nude mice to detect the treatment effect of 5-Fluoracil combined with curcumin in vivo. Results: It was revealed that curcumin could inhibit the glycolysis in the endometrial cancer cells, but the OXPHOS level couldn’t be changed. It was also found that curcumin could down-regulate the expression of pyruvate dehydrogenase kinase-2 (PDK2), which regulated the process of glycolysis. The knock-downed expression of PDK2 by specific shRNA decreased the level of glycolysis and proliferation of endometrial cancer cells. Curcumin could inhibit the level of glycolysis in the endometrial cancer cells by down-regulating the expression of PDK2. Combined with 5-FU, curcumin could obviously increase the sensitivity of endometrial cancer cells to chemotherapeutics, and up-regulate the ability to inhibit the proliferation of cancer cells. Conclusion: Curcumin could inhibit the expression of PDK2 and the level of glycolysis in the endometrial cancer cells. As a result, curcumin could obviously increase the sensitivity to 5-FU, and inhibit the proliferation of endometrial cancer cells effectively.

Key words： endometrial cancer glycolysis curcumin pyruvate dehydrogenase kinase-2 5-fluorouracil

Received: 20 February 2019

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	JIN Weiwei
	LIN Yihe
	ZHAO Xiaoying
	ZHUANG Xiaoping
	CAI Pingsheng

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https://xb.wmu.edu.cn/EN/10.3969/j.issn.2095-9400.2019.12.005 OR https://xb.wmu.edu.cn/EN/Y2019/V49/I12/878

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