缝隙连接蛋白43组成的缝隙连接对依托泊苷抗肿瘤作用的影响

发布时间：2018-08-26 13:56

【摘要】：背景与目的:缝隙连接能够增强化疗药物的细胞毒性,但缝隙连接蛋白43(connexin 43,Cx43)组成的缝隙连接对依托泊苷抗肿瘤作用的影响尚不清楚。因此,本研究拟观察睾丸癌细胞中Cx43对依托泊苷抗肿瘤作用的影响。方法:采用细胞接种荧光示踪实验检测睾丸癌细胞由Cx43形成的缝隙连接通讯功能,同时检测不同的药物(18-α-甘草次酸及维甲酸)和Cx43干扰RNA对缝隙连接功能的影响;采用标准细胞集落形成分析法检测睾丸癌细胞中由Cx43形成的缝隙连接通讯功能改变后,对依托泊苷抑制肿瘤细胞生长作用的影响。结果:荧光示踪实验显示18-α-甘草次酸可显著降低缝隙连接通讯功能,而维甲酸则可增强缝隙连接功能;Cx43干扰RNA能够显著抑制缝隙连接功能。标准细胞集落形成实验结果表明,在缝隙连接形成的睾丸癌细胞中,18-α-甘草次酸显著降低依托泊苷对睾丸癌细胞生长的抑制作用,而维甲酸则增强依托泊苷对睾丸癌细胞生长的抑制作用;应用Cx43干扰RNA能够显著降低依托泊苷对睾丸癌细胞生长的抑制作用。结论:睾丸癌细胞中Cx43形成的缝隙连接通讯功能降低能够减弱依托泊苷的抗肿瘤作用;而缝隙连接通讯功能增强能够增强其抗肿瘤作用。
[Abstract]:Background & AIM: gap junction can enhance the cytotoxicity of chemotherapeutic drugs, but the effect of gap junction composed of connexin 43 (connexin 43) on etoposide's antitumor effect is not clear. Therefore, the aim of this study was to investigate the effect of Cx43 on etoposide in testicular cancer cells. Methods: the gap junction communication function of testicular cancer cells formed by Cx43 was detected by cell inoculation fluorescence tracer test. The effects of different drugs (18- 伪 -glycyrrhetinic acid and retinoic acid) and Cx43 interfering RNA on gap junction function were also detected. Standard cell colony forming assay was used to detect the effect of etoposide on the inhibition of tumor cell growth after the change of gap junction communication function formed by Cx43 in testicular cancer cells. Results: fluorescence tracer test showed that 18- 伪 -glycyrrhetinic acid could significantly reduce gap junction communication function, while retinoic acid could enhance gap junction function. Cx43 interference RNA could significantly inhibit gap junction function. The results of standard cell colony formation test showed that 18- 伪 -glycyrrhetinic acid significantly decreased the growth inhibition of etoposide in testicular cancer cells formed by gap junction. The inhibitory effect of etoposide on the growth of testicular cancer cells was enhanced by retinoic acid, and the inhibitory effect of etoposide on the growth of testicular cancer cells was significantly decreased by Cx43 interference with RNA. Conclusion: the decrease of gap junction communication function formed by Cx43 in testicular cancer cells can attenuate the antineoplastic effect of etoposide, and the enhancement of gap junction communication function can enhance the antitumor effect of etoposide.
【作者单位】：广州医科大学附属第二医院麻醉科;广东省中医院肝胆外科;中山大学中山医学院;
【基金】：国家自然科学基金资助项目(81401017) 广州市卫生局西医引导项目(20141A011083)
【分类号】：R96

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