趋化因子CCL18调控LDHA、LDHB促进前列腺癌细胞糖酵解的机制研究

肿瘤糖代谢一直是肿瘤发展及治疗领域的研究热点，乳酸脱氢酶（LDH）是糖代谢的关键酶。我们已证实CCL18促进前列腺癌发生、发展，与前列腺癌预后密切相关（Bio Med Int, 2014）：预实验发现CCL18上调LDHA、下调LDHB表达，促进乳酸形成；应用组织芯片发现LDHA、LDHB在前列腺癌与非癌中存在差异性表达并与疾病预后相关，同时LDHA\LDHB比值在良性前列腺疾病及前列腺癌的前列腺液、组织中均存在表达差异。但CCL18调控LDHA、LDHB影响前列腺癌糖酵解的机制是什么？据此，我们提出CCL18信号通路调控LDHs参与前列腺癌细胞糖酵解的假设。拟通过CRISPR/Cas9 技术构建实验细胞株，建立小鼠模型，揭示CCL18通路调控糖酵解的机制，通过临床数据相关性分析评估LDHs对前列腺癌诊疗的临床意义，为前列腺癌的糖代谢靶向治疗提供可靠依据。

The glycolysis of tumor has been a hotspot in the field of tumor development and treatment.Lactate dehydrogenase (LDH) is the tetramer emzyme, which composed of two major subunits called LDHA and LDHB, is the key enzyme of glycolytic pathway. Our previous study proved that CCL18 is closely related to the occurrence, development and prognosis of prostate cancer (Bio Med Int, 2014), and in the preliminary experiments found that CCL18 up-regulated LDHA but down-regulated expression, and raised the lactate level. Our TMA data showed that LDHA and LDHB were differential expression between prostate cancer and non-cancerous prostatic tissues which were related to prognosis of prostate cancer. Whether CCL18 involved in prostate cancer cells glycolysis? On this basis, we hypothesized that CCL18 regulating the LDHs expression pattern which may involved in prostate cancer cells glycolysis. CRISPR/Cas9 technology was utilized to establish LDHA ko and LDHB ko cell lines and mice models to elucidate the molecular mechanism of how CCL18 involved in regulating the glycolysis pathway. A further analysis of clinical data correlation which LDHs is needed to assess clinical significance of prostate cancer diagnosis and treatment. And we hope to provide a reliable evidence for a new targeted therapy with metabolism in prostate cancer.