| 张 磊,樊扬威,胡 媛,井佳瑜,师 煜,李恩孝.肿瘤相关巨噬细胞对肾透明细胞癌增殖作用及其分子机制的影响[J].现代生物医学进展英文版,2019,19(17):3225-3229. |
| 肿瘤相关巨噬细胞对肾透明细胞癌增殖作用及其分子机制的影响 |
| Sunitinib inhibits PDPK1-mediated PKG1 Phosphorylation and Inhibits Proliferation of Renal Clear Cell Carcinoma by Inhibiting Macrophage Secretion of IL-6 |
| Received:March 21, 2018 Revised:April 18, 2018 |
| DOI：10.13241/j.cnki.pmb.2019.17.005 |
| 中文关键词: 巨噬细胞 透明细胞癌 IL-6 PDPK1 PKG1 |
| 英文关键词: Macrophages Clear cell carcinoma IL-6 PDPK1 PKG1 |
| 基金项目:陕西省自然科学基金项目(2017SZ3428JGF0) |
| Author Name | Affiliation | E-mail | | ZHANG Lei | Department of Onalogy, Xi'an Jiaotong University, Xi'an, Shaanxi, 715300, China | 2814617272@qq.com | | FAN Yang-wei | Department of Onalogy, Xi'an Jiaotong University, Xi'an, Shaanxi, 715300, China | | | HU Yuan | Department of Onalogy, Xi'an Jiaotong University, Xi'an, Shaanxi, 715300, China | | | JING Jia-yu | Department of Onalogy, Xi'an Jiaotong University, Xi'an, Shaanxi, 715300, China | | | SHI Yu | Department of Onalogy, Xi'an Jiaotong University, Xi'an, Shaanxi, 715300, China | | | LI En-xiao | Department of Onalogy, Xi'an Jiaotong University, Xi'an, Shaanxi, 715300, China | |
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| 中文摘要: |
| 摘要 目的：探讨肿瘤相关巨噬细胞（Tumor Associated Macrophages, TAMs）对肾透明细胞癌的增殖影响及其分子机制。方法：将单核细胞系(THP-1)细胞诱导为 TAMs，同时采用细胞共培养方法将TAMs和肾透明细胞癌ACHN共培养，共培养前后舒尼替尼给药处理；CCK-8和克隆形成实验检测共培养前后ACHN细胞增殖能力；TAMs和ACHN细胞共培养，采用皮下接种方法建立裸鼠皮下移植瘤模型，舒尼替尼给药处理，观察裸鼠皮下成瘤能力及肿瘤体积大小；Western Blot检测共培养前后磷酸肌醇依赖性蛋白激酶1 (Phosphoinositol Dependent Protein Kinase 1，PDPK1)介导磷酸甘油酸激酶1(Phosphoglycerate Kinase 1, PKG1)的磷酸化作用的影响。结果：显微镜观察结果显示肿瘤相关巨噬细胞促进了ACHN细胞增殖作，而舒尼替尼可以抑制其促增殖作用；CCK-8和克隆形成实验表明TAMs促进了ACHN克隆形成能力，但是其克隆形成能力可以被舒尼替尼抑制；动物实验证明TAMs促进裸鼠皮下成瘤能力和移植瘤的成长；肿瘤相关巨噬细胞可以通过分泌IL-6促进PDPK1介导PKG1的磷酸化。结论：肿瘤相关巨噬细胞通过分泌IL-6促进PDPK1介导PKG1的磷酸化作用，从而促进了肾透明细胞癌的增殖作用。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect of Tumor Associated Macrophages (TAMs) on the proliferation of renal clear cell carcinoma (RCCC) and its molecular mechanism. Methods: Monocyte line (THP-1) cells were induced into TAMs, and TAMs and ACHN were co-cultured with clear cell carcinoma of kidney (RCC) by cell co-culture method, then treated with sunitinib before and after co-culture; CCK-8 and clone formation assay were used to detect the proliferation of ACHN cells before and after co-culture; TAMs and ACHN cells were co-cultured with subcutaneous inoculation method to establish subcutaneous transplanted tumor model in nude mice, where sunitinib was administered. Western Blot was used to detect the effect of Phosphoinositol Dependent Protein Kinase 1 (PDPK1) on phosphorylation of Phosphoglycerate Kinase 1(PKG1) before and after co-culture. Results: Microscopic observation showed that tumor-related macrophages promoted the proliferation of ACHN cells, while sunitinib inhibited the proliferation of ACHN cells; CCK-8 and clonogenesis experiments showed that TAMs promoted the clonogenic ability of ACHN, but its clonogenic ability could be inhibited by sunitinib; animal experiments showed that TAMs promoted the growth of subcutaneous tumors and transplanted tumors in nude mice.Tumor-related macrophages can promote the phosphorylation of PKG1 mediated by PDPK1 by secreting IL-6. Conclusion: Tumor-related macrophages promote the phosphorylation of PKG1 mediated by PDPK1 through secreting IL-6, thus promoting the proliferation of renal clear cell carcinoma. |
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