TRPM7通过钙信号调控糖代谢重编程参与卵巢癌铂耐药机制研究

卵巢癌死亡率居女性生殖系统恶性肿瘤之首，70%患者发现即为晚期，一线治疗面临复发，多线化疗出现耐药，铂耐药是导致疗效差的关键。我们前期发现TRPM7通过钙信号介导EMT促进卵巢癌转移，并发现可影响卵巢癌细胞糖代谢，且在卵巢癌铂耐药组织中TRPM7明显高表达，提示TRPM7可能通过调控糖代谢重编程参与卵巢癌铂耐药。本项目将在前期研究基础上，通过构建卵巢癌铂耐药细胞株及PDX模型，从体内外多角度研究TRPM7对卵巢癌细胞糖代谢重编程的调控作用及与卵巢癌铂耐药相关性，探讨TRPM7通过[Ca2+]i-MAPK-c-Myc信号轴调控糖代谢重编程参与卵巢癌铂耐药的分子机制。通过本项目的研究，将阐明TRPM7调控糖代谢重编程参与卵巢癌铂耐药的机制，从代谢角度为卵巢癌化疗增敏和逆转铂耐药提供新靶点和理论依据。

Ovarian cancer mortality rate ranks the first among female reproductive system malignant tumors. About 70% of patients were in late stages when they were first diagnosed. First-line treatment is easy recurrence, and multiline chemotherapy is resistant. Platinum resistance is the key to poor curative effect. Previously, we found that TRPM7 mediated EMT and promotes ovarian cancer metastasis by calcium signal, and affect the glycometabolism. Moreover, TRPM7 is highly expressed in platinum-resistant tissues of ovarian cancer, suggesting that TRPM7 may participate in platinum-resistant ovarian cancer by regulating glycometabolism reprogramming. On the basis of previous studies, this project will construct platinum-resistant ovarian cancer cell lines and PDX models, study the regulation of TRPM7 on the glycometabolism reprogramming of ovarian cancer cells in vitro and in vivo, and explore the correlation between TRPM7 and platinum-resistant ovarian cancer cells, which will explore the molecular mechanism of TRPM7 regulating glycometabolism reprogramming through [Ca2+]i-MAPK-c-Myc signal axis in platinum-resistant ovarian cancer. We will elucidate the mechanism of TRPM7 regulating glycometabolism reprogramming in platinum resistant ovarian cancer, and provide new targets and theoretical basis for enhancing chemosensitivity and reversing platinum resistance of ovarian cancer.