摘要: |
[摘要] 目的 探讨Garcinone C对鼻咽癌细胞溶酶体损伤的影响及相关机制。方法 选择鼻咽癌细胞HONE1和S18进行实验,以Garcinone C进行干预处理。采用CCK-8实验检测细胞增殖活力,通过磷酸酯法检测酸性磷酸酶活性。采用免疫荧光实验检测溶酶体膜蛋白1(LAMP1)、半乳糖凝集素-3(Gal-3)、组织蛋白酶D(CTSD)的表达量,并观察其定位。通过Western blot实验检测CTSD、LAMP1、Gal-3、Ras相关蛋白Rab-7a(Rab7a)、囊泡相关膜蛋白8(VAMP8)的表达水平。结果 Garcinone C可抑制鼻咽癌细胞活力及酸性磷酸酶活性(P<0.05),促进胞质中LAMP1、Gal-3、CTSD表达量上升(P<0.05)。经Garcinone C干预后,鼻咽癌细胞CTSD、LAMP1、Gal-3、Rab7a蛋白表达水平显著上升(P<0.05),VAMP8蛋白表达水平显著下降(P<0.05),且调控作用呈剂量依赖性。结论 Garcinone C可能通过损伤鼻咽癌细胞溶酶体发挥治疗作用,有望成为鼻咽癌化疗药物开发的候选先导化合物。 |
关键词: Garcinone C 鼻咽癌 溶酶体损伤 |
DOI:10.3969/j.issn.1674-3806.2025.04.08 |
分类号: |
基金项目:国家自然科学基金项目(编号:82260721,81903644);广西自然科学基金重点项目(编号:2024GXNSFDA010045);广西医科大学大学生创新训练计划项目(编号:202310598054) |
|
A study on effects of Garcinone C on lysosomal damage of nasopharyngeal carcinoma cells and their related mechanisms |
DAI Yiping1, YIN Fuqiang2, WANG Chunlai1, SUN Xuemei1, ZHANG Jinyan3, LIU Xia1
|
1.School of Basic Medical Sciences, Key Laboratory of Longevity and Aging-Related Disease of Chinese Ministry of Education, Guangxi Medical University, Nanning 530021, China; 2.Life Sciences Institute, Guangxi Medical University, Nanning 530021, China; 3.Guangxi Medical University College of Stomatology, Nanning 530021, China
|
Abstract: |
[Abstract] Objective To explore the effects of Garcinone C on lysosomal damage of nasopharyngeal carcinoma(NPC) cells and their related mechanisms. Methods NPC cells HONE1 and S18 were selected for experiment, and Garcinone C was used as intervention treatment. CCK-8 assay was used to detect cell proliferation viability, and the phosphate ester method was used to detect acid phosphatase activity. The expression levels of lysosomal-associated membrane protein 1(LAMP1), galectin-3(Gal-3) and cathepsin D(CTSD) were detected by using immunofluorescence assay, and their localizations were observed. The expression levels of CTSD, LAMP1, Gal-3, Ras-related protein Rab-7a(Rab7a) and vesicle-associated membrane protein 8(VAMP8) were detected by using Western blot. Results Garcinone C could inhibit the viability of NPC cells and the activity of acid phosphatase(P<0.05), and promote an increase in the expression levels of LAMP1, Gal-3 and CTSD in the cytoplasm(P<0.05). After intervention with Garcinone C, the expression levels of CTSD, LAMP1, Gal-3 and Rab7a proteins in NPC cells were significantly increased(P<0.05), while the expression level of VAMP8 protein was significantly decreased(P<0.05). These regulatory effects were dose-dependent. Conclusion Garcinone C may play a therapeutic role by damaging lysosomes of NPC cells. Garcinone C is expected to be a candidate lead compound in the development of chemotherapy drugs for NPC. |
Key words: Garcinone C Nasopharyngeal carcinoma Lysosomal damage |