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目的:探讨SOX4与食管癌顺铂耐药的关系及其耐药机制。方法:采用递增药物浓度、间歇冲击作用的方法构建顺铂食管癌耐药细胞株KYSE30/DDP;流式细胞仪检测KYSE30及KYSE30/DDP细胞凋亡情况;Western blot检测SOX4及凋亡相关指标在KYSE30及KYSE30/DDP细胞中的变化;CCK8检测干扰SOX4对KYSE30和KYSE30/DDP细胞顺铂敏感度的影响;流式细胞仪及Western blot检测干扰SOX4对KYSE30/DDP细胞凋亡及相关指标的影响。结果:成功构建了生长状态良好的KYSE30/DDP细胞株,其耐药指数为4.1;KYSE30/DDP细胞凋亡较其亲本细胞KYSE30明显降低(t=-8.414,P<0.05);Western blot结果显示,SOX4在顺铂耐药细胞KYSE30/DDP中的表达高于其亲本细胞KYSE30,KYSE30/DDP细胞中凋亡相关指标Cleaved caspase-3及Cleaved PARP表达低于KYSE30;在KYSE30/DDP细胞中干扰SOX4,其对顺铂的敏感性及凋亡细胞增加(F=625.423,P<0.05),凋亡相关指标Cleaved caspase-3及Cleaved PARP表达增加。结论:SOX4在食管癌顺铂耐药细胞KYSE30/DDP中高表达,并可通过抑制凋亡介导食管癌顺铂耐药。
Objective: To investigate the relationship between drug-resistance of SOX4 and cisplatin-resistant esophageal cancer and its mechanism of drug resistance. Methods: The cisplatin-resistant esophageal cancer cell line KYSE30 / DDP was constructed by increasing drug concentration and intermittent impact. The apoptosis of KYSE30 and KYSE30 / DDP cells was detected by flow cytometry. The expressions of SOX4 and apoptosis-related index KYSE30 and KYSE30 / DDP cells. CCK8 was used to detect the influence of SOX4 on cisplatin sensitivity of KYSE30 and KYSE30 / DDP cells. Flow cytometry and Western blot were used to detect the effects of SOX4 on apoptosis and related indexes of KYSE30 / DDP cells . Results: The KYSE30 / DDP cell line with good growth status was successfully constructed and its resistance index was 4.1. The apoptosis rate of KYSE30 / DDP cells was significantly lower than that of KYSE30 cells (t = -8.414, P <0.05) , And the expression of SOX4 in KYSE30 / DDP cells was higher than that of KYSE30 in KDR cells. The expression of Cleaved caspase-3 and Cleaved PARP in KYSE30 / DDP cells was lower than that in KYSE30. The interference of SOX4 in KYSE30 / DDP cells , And its sensitivity to cisplatin and apoptotic cells increased (F = 625.423, P <0.05), and the expression of Cleaved caspase-3 and Cleaved PARP increased. Conclusion: SOX4 is overexpressed in cisplatin-resistant cell KYSE30 / DDP esophageal cancer cells and can induce cisplatin-resistant esophageal cancer by inhibiting apoptosis.