喹啉衍生物PQ1联合顺铂对前列腺癌PC3细胞的增殖及细胞缝隙连接通讯的影响

Quinoline derivative PQ1 combined with cisplatin promotes the proliferation and gap junction communication of prostate cancer PC3 cells

目的：探讨喹啉衍生物PQ1联合顺铂对前列腺癌PC3细胞的增殖及细胞缝隙连接通讯的影响。方法：体外培养前列腺癌PC3细胞,对比空白对照组、10 mg/ml顺铂对照组及顺铂联合不同浓度（1、2、5、10、15μmol/L）喹啉衍生物PQ1各组PC3细胞增殖情况,通过RT-PCR法及Western印迹法检测各组间细胞缝隙连接相关蛋白Cx43 mRNA及蛋白表达情况。结果：喹啉衍生物PQ1浓度在1~10μmol/L联合顺铂能明显抑制PC3细胞的体外增殖,随浓度、时间的增加,抑制率相应升高。不同浓度联合药物处理PC3细胞后,Cx43 mRNA及蛋白表达也有不同程度升高。结论：喹啉衍生物可以通过上调前列腺癌PC3细胞间缝隙连接相关蛋白Cx43 mRNA及蛋白的表达水平来促进前列腺癌PC3细胞的细胞间缝隙连接功能,增强顺铂对前列腺癌PC3细胞的杀伤作用。

Objective： To investigate the effects of the quinoline derivative PQ1 combined with cisplatin on the proliferation and gap junction communication of prostate cancer PC3 ceils. Methods ： We cultured in vitro prostate cancer PC3 cells and divided them into DMSO blank control, cisplatin control, and cisplatin （10 mg/ml） plus PQ1 （1, 2, 5, 10, and 15 μmol/L） groups. We meas- ured the proliferation of the prostate cancer PC3 cells, determined the expressions of the connexin 43 （ Cx43 ） mRNA and protein by RT-PCR and Western blot, and compared the indexes among different groups. Results： Cisplatin combined with PQ1 at 1 - 10 μmol/L significantly inhibited the proliferation of the PC3 cells and the inhibition rate rose in a concentration- and time-dependent manner, from （48.72 ± 0.98） % vs （50.33 ± 0.62） % at 0 μmol/L to （77.38 ± 1.12） % vs （83.50 ± 1.05 ） % at 15 μmoL/L at 24 and 48 hours （P 〈0.05）. Compared with the cisplatin control, cisplatin combined with PQ1 at 1, 2, 5, 10, and 15 μmoL/L in- creased the expression of Cx43 mRNA from 0. 379 ±0. 113 to 0. 669 ±0. 031, 0. 831 ±0. 127, 0. 769 ±0. 100, 0. 532 ±0. 086, and 0.475 ±0. 134, respectively （P 〈 0.05 ） , and cisplatin combined with PQ1 at 1,2, 5, and 10 μmol/L elevated that of Cx43 protein from0.138±0.146 to0.263±0.111,0.306±0. 152, 0.415±0.280, and 0.643 ±0.310, respectively （P〈0.05）. Conclu- sion： The quinoline derivative PQ1 can promote the gap junction communication of prostate cancer PC3 cells and enhance the killing effect of cisplatin on PC3 cells by upregulating the expressions of Cx43 mRNA and protein.