|国家科技期刊平台
首页|期刊导航|中国病理生理杂志|双氢青蒿素通过激活氯通道促进鼻咽癌CNE-2Z细胞放疗敏感性

双氢青蒿素通过激活氯通道促进鼻咽癌CNE-2Z细胞放疗敏感性OA北大核心CSTPCD

Dihydroartemisinin promotes radiotherapy sensitivity of nasopharyngeal carcinoma CNE-2Z cells by activating chloride channels

中文摘要英文摘要

目的:探讨ClC-3氯通道在双氢青蒿素(DHA)促进鼻咽癌CNE-2Z细胞放射增敏中的作用.方法:MTT法检测DHA对CNE-2Z细胞和正常鼻咽上皮NP69-SV40T细胞活力的抑制作用;集落形成实验检测DHA对CNE-2Z细胞的放射增敏作用;Western blot检测ClC-3蛋白的表达;siRNA技术下调ClC-3蛋白的表达;全细胞膜片钳技术记录细胞氯电流.结果:(1)相较于NP69-SV40T细胞,DHA可选择性抑制CNE-2Z细胞活力,IC10值分别为(13.020±4.831)μmol/L和(5.244±1.050)μmol/L(P<0.01);(2)集落形成实验结果显示,DHA对CNE-2Z细胞具有放疗增敏作用,放射增敏比为1.9;(3)DHA能激活CNE-2Z细胞的氯通道,产生外向氯电流;但对NP69-SV40T细胞的氯通道则无影响;(4)DHA促进CNE-2Z细胞的ClC-3氯通道蛋白的表达(P<0.01);(5)氯通道阻断剂NPPB可抑制DHA对CNE-2Z细胞的放射增敏作用,抑制比达1.84;同时也抑制DHA激活的氯电流;(6)下调CNE-2Z 的ClC-3蛋白可抑制DHA对鼻咽癌CNE-2Z细胞的放射增敏作用,抑制比达4.19;DHA对CNE-2Z细胞的氯电流的激活作用则不再产生.结论:DHA对鼻咽癌CNE-2Z细胞产生放疗增敏作用,很可能与ClC-3氯通道被激活有关.

AIM:To investigate the role of ClC-3 chloride channel in the promotion of radio sensitization of na-sopharyngeal carcinoma CNE-2Z cells by dihydroartemisinin(DHA).METHODS:MTT was used to detect the inhibito-ry effect of DHA on the viability of CNE-2Z cells and normal nasopharyngeal epithelial NP69-SV40T cells,the radio sensi-tization effect of DHA on CNE-2Z cells was detected by cloning assay,the expression of ClC-3 protein was detected by Western blot,the expression of ClC-3 protein was down-regulated by siRNA technology,and the chlorine current of cells was recorded by whole cell patch-clamp technology.RESULTS:(1)Compared with NP69-SV40T cells,DHA selective-ly inhibited the proliferation of CNE-2Z cells,with IC10 values of(13.020±4.831)μmol/L and(5.244±1.050)μmol/L,respectively(P<0.01).(2)The results of clonal formation experiments showed that DHA had a radio sensitizing effect on CNE-2Z cells,with a radio sensitization ratio of 1.9.(3)DHA could activate the chlorine channel of CNE-2Z cells and produce an outward chlorine current,but had no effect on the chlorine channel of NP69-SV40T cells.(4)DHA promoted the expression of ClC-3 chloric channel protein in CNE-2Z cells(P<0.01).(5)Chlorine channel blocker NPPB could in-hibit the radio sensitizing effect of DHA on CNE-2Z cells by 1.84 times,and also inhibited the chlorine current activated by DHA.(6)the down-regulation of CNE-2Z ClC-3 protein could inhibit the radio sensitization effect of DHA on CNE-2Z cells by 4.19 times,and the activation of chlorine current by DHA on CNE-2Z cells was no longer produced.CONCLU-SION:DHA has a radio sensitizing effect on nasopharyngeal carcinoma CNE-2Z cells,which is likely to be related to the activation of ClC-3 chloride channel.

刘世情;周丛然;唐鑫伟;周汉芬;李雪苛;侯秀颖;杨海峰;朱林燕

暨南大学基础医学与公共卫生学院药理学系,广东 广州 510632广州华商学院,广东 广州 511300广东省中医院大学城医院放射科,广东 广州 510006广东省中医院病理科,广东 广州 510120

临床医学

鼻咽癌双氢青蒿素放射增敏ClC-3氯通道

nasopharyngeal carcinomadihydroartemisininradiation sensitizationClC-3 chloride channels

《中国病理生理杂志》 2024 (002)

255-264 / 10

国家自然科学基金资助项目(No.81872133)

10.3969/j.issn.1000-4718.2024.02.008

评论