[1]蒋国君,刘亚明,赵婉晨,等.雌激素受体阳性的乳腺癌细胞缝隙连接的调控对阿霉素抗肿瘤作用的影响[J].南方医科大学学报,2018,(07):780.
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雌激素受体阳性的乳腺癌细胞缝隙连接的调控对阿霉素抗肿瘤作用的影响()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2018年07期
页码:
780
栏目:
出版日期:
2018-07-16

文章信息/Info

Title:
Effect of gap junction modulation on antitumor effects of adriamycin in estrogen receptor-positive breast cancer cells
作者:
蒋国君刘亚明赵婉晨王道鑫董淑英童旭辉
关键词:
乳腺癌缝隙连接维甲酸油酸酰胺阿霉素
Keywords:
breast cancer gap junctions retinoic acid oleamide adriamycin
摘要:
目的在雌激素受体阳性的乳腺癌细胞MCF-7中观察缝隙连接(GJ)功能的调控对阿霉素抗肿瘤作用的影响。方法采用 MTT法检测0~24.0 μmol/L 阿霉素对细胞存活率的影响;Western blot和细胞免疫荧光法分别检测细胞中Cx43总蛋白和膜蛋白 的表达;细胞接种荧光示踪法检测细胞缝隙连接功能;采用维甲酸增强细胞GJ功能,油酸酰胺和18-alpha-甘草次酸(18-α-GA) 抑制细胞GJ功能;Cx43siRNA沉默细胞中Cx43基因。结果雌激素受体阳性(ER+)细胞中Cx43表达水平及GJ功能显著强于 雌激素受体阴性ER(-)细胞,阿霉素显著抑制MCF-7细胞的增殖(P<0.01),维甲酸可以通过增加细胞GJ功能从而增强阿霉素 的细胞毒性(P<0.01),油酸酰胺和18-α-GA可通过抑制细胞GJ功能而降低阿霉素的细胞毒性(P<0.01);采用siRNA沉默细胞 Cx43基因,胞内Cx43总蛋白和膜蛋白表达下降,GJ功能降低,阿霉素对MCF-7的细胞毒性降低(P<0.01)。结论ER(+)细胞中 Cx43表达水平及GJ功能显著强于ER(-)细胞;维甲酸可以通过增强细胞GJ功能而增加阿霉素细胞毒性,油酸酰胺和18-α-GA 通过抑制细胞GJ功能降低阿霉素细胞毒性,Cx43siRNA能沉默MCF-7中Cx43表达,并抑制由其形成的GJ功能,降低阿霉素的 细胞毒性。
Abstract:
Objective To observe the effect of functional modulation of gap junctions (GJ) on the antitumor effect of adriamycin in breast cancer cells positive for estrogen receptor (ER). Methods The inhibitory effect of 0 to 24.0 μmol/L adriamycin on the surviving fraction of ER-positive human breast cancer MCF-7 cells and ER-negative MDA-MB-231 cells was assessed with MTT assay; Western blotting and immunofluorescence assay were used to detect the expressions of Cx43 total protein and membrane protein in the cells. A parachute assay was used to evaluate the function of the GJ in MCF-7 cells. The cytotoxic effect of adriamycin was observed in the cells treated with retinoic acid (RA) for enhancing GJ function, in cells treated with oleamide and 18-alpha- glycyrrhizic acid (18-alpha-ga) for inhibiting GJ function, and also in cells transfected with Cx43siRNA for Cx43 knockdown. Results ER-positive MCF-7 cells expressed a significantly higher level of Cx43 with stronger GJ function than ER-negative MDA- MB-231 cells. Adriamycin significantly inhibited the proliferation of MCF-7 cells (P<0.01), and RA treatment further increased the cytotoxicity of adriamycin (P<0.01) while oleamide and 18-α-GA obviously attenuated the cytotoxicity of adriamycin (P<0.01). In the cells with Cx43 knockdown, the expressions of total Cx43 protein and Cx43 on the membrane were significantly reduced, the function of GJ was attenuated, and the cytotoxicity of adriamycin was significantly decreased (P<0.01). Conclusions ER-positive breast cancer cells have stronger Cx43 expressions and GJ function than the ERnegative cells. The cytotoxicity of adriamycin against the breast cancer cells can be strengthened by enhancing GJ function and attenuated by inhibiting GJ function. Cx43 silencing inhibits the function of GJ to lower the cytotoxicity of adriamycin in human breast cancer MCF-7 cells.

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更新日期/Last Update: 1900-01-01